Previous Article | Next Article 
Clinical and Diagnostic Laboratory Immunology, March 2000, p. 161-167, Vol. 7, No. 2
Laboratoire de Pathologie Infectieuse et
Immunologie, INRA, Tours-Nouzilly, France
Received 24 June 1999/Returned for modification 18 October
1999/Accepted 15 November 1999
The prompt recruitment of neutrophils to the site of infection is
essential for the defense of the bovine mammary gland against invading
pathogens and is determinant for the outcome of the infection. Escherichia coli is known to induce clinical mastitis,
characterized by an intense neutrophil recruitment leading to the
eradication of the bacteria, whereas Staphylococcus aureus
induces subclinical mastitis accompanied by a moderate neutrophil
recruitment and the establishment of chronic mastitis. To elicit the
neutrophil recruitment into the udder, inflammatory mediators must be
produced after recognition of the invading pathogen. To our knowledge, those mediators have never been studied during S. aureus
mastitis, although understanding of the neutrophil recruitment
mechanisms could allow a better understanding of the differences in the
pathogeneses elicited by E. coli and S. aureus.
Therefore, we studied, at several time points, the accumulation of
neutrophils and the presence of the chemoattractant complement fragment
C5a and of the cytokines interleukin-1 An acute inflammatory reaction is
crucial in the defense of host tissue against invading pathogens.
Leukocytes, especially neutrophils, are the major contributors to this
mechanism of natural defense, and their migration to the site of
infection is determinant for the outcome of the infection. Neutrophil
migration is elicited by inflammatory mediators which are produced in
the infected tissue by cells responding to bacterial toxins or
metabolites. The array of known inflammatory mediators is vast and
includes complement fragments, arachidonic acid metabolites, vasoactive
amines, and cytokines. Cytokines mediate the leukocyte recruitment to
inflammatory sites by their chemotactic activity and by activation of
adhesion molecules on circulating leukocytes and endothelial cells in
adjacent vasculature (5, 22). Several cytokines, including
interleukin 1 Inflammation of the mammary gland caused by invading pathogens is
common among lactating dairy cows and is a major cause of economic
losses (8). The mammary gland is particularly suited to
investigations on the inflammatory response to infection at an
epithelial surface, because it lends itself to kinetic studies of the
appearance of inflammatory cells and mediators in the luminal compartment as a result of the ease of noninvasive and repeated samplings of milk. Bovine mastitis is of two types, i.e., (i) clinical
or (ii) subclinical with eventual sporadic clinical episodes. Escherichia coli causes severe mastitis, during which death
or extensive damage to mammary tissues may result (11, 20).
When the cow survives, the clinical episode is followed by a
spontaneous bacteriological cure (19). In contrast,
Staphylococcus aureus infection often starts with an acute
phase and generally becomes chronic and subclinical (44).
These opposed characteristics are likely to result from the different
pathogenic mechanisms used by the two pathogens. Among these
mechanisms, the role of bacterial adherence is a controversial topic
(2, 14, 17). It has been suggested that adhesion is
important for the virulence of S. aureus but not for
E. coli, which multiplies rapidly within the milk
compartment between milkings (19). Moreover, S. aureus expresses several specific virulence factors such as
protein A and a capsule or a pseudocapsule (slime), which are
antiphagocytic factors, and toxins (alpha and beta) which appear to
play a major role in the staphylococcal virulence (44). On
the other hand, E. coli releases endotoxins
(lipopolysaccharide [LPS]-protein complexes) that appear to be
the primary initiator of inflammation (23). Although LPS is
not a chemoattractant for bovine neutrophils (7, 16), it can
induce the production of cytokines, one of which, IL-1, mediates many
of the biologic responses to LPS, including fever and the acute-phase
response (10, 15).
The differences in the proposed pathogenesis and clinical reactions
offer the opportunity to contrast two inflammatory responses which have
different outcomes: the inflammatory reaction allows the eradication of
E. coli and a bacteriological cure, whereas in S. aureus infection, bacteria are persistent in the udder and a
chronic infection develops.
This work was designed to compare the early host responses to E. coli and S. aureus intramammary infections by measuring
inflammatory markers (bovine serum albumin [BSA] and haptoglobin) and
inflammatory mediators involved in neutrophil recruitment (TNF- Animals.
Eleven clinically healthy Holstein cows in
midlactation were experimentally infected in one randomly selected
mammary gland. Quarters were determined to be free of bacterial
infection prior to challenge upon bacteriological analyses. In
experiment 1, five cows were challenged with E. coli. In
experiment 2, the other six cows were challenged with S. aureus.
Bacterial challenge.
E. coli strain P4 and S. aureus strain 107-59 were isolated from natural cases of bovine
mastitis (6, 31). The bacteria were cultivated in a brain
heart infusion medium (Difco Laboratories, Detroit, Mich.) at 37°C
for 5 to 6 h to allow them to be in the exponential growth phase.
They were then harvested, washed once in pyrogen-free saline (PFS) and
suspended in PFS. The optical density at 550 nm was measured, and the
number of CFU was determined using a standard curve. After appropriate
dilution in PFS, 0.2 ml of the bacterial suspension (~50 CFU of
E. coli and 50 to 100 CFU of S. aureus in
experiment 1 and experiment 2, respectively) was injected in the
challenged glands via the teat canal immediately after the evening milking.
Samples.
Just before the inoculation of the bacteria,
foremilk and blood samples were collected and rectal temperatures were
measured. After E. coli infusion, rectal temperatures and
blood samples were obtained at 8, 12, 14, 16, 24, 48, and 72 h
postinfusion (p.i.) and at 4, 8, and 14 days p.i., and sterile foremilk
samples were collected at 4, 6, 8, 10, 12, 14, 16, 18, 24, 39, 48, 63, and 72 hours p.i. and at 4, 8, and 14 days p.i. After S. aureus infusion, rectal temperatures and blood and sterile
foremilk samples were obtained once a day from day 1 to 5 p.i. and
then at 7, 11, 14, 21, and 28 days p.i.
1071-412X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Differential Induction of Complement Fragment C5a and
Inflammatory Cytokines during Intramammary Infections with
Escherichia coli and Staphylococcus
aureus
ABSTRACT
Top
Abstract
Introduction
Materials and Methods
Results
Discussion
References
(IL-1), tumor necrosis
factor alpha, and IL-8 in milk after inoculation of E. coli
or S. aureus in lactating bovine udders. The low levels of
C5a and the absence of cytokines in milk from S. aureus-infected cows, compared to the high levels found in milk
from E. coli-infected animals, mirror the differences in
the severities of the two inflammatory reactions. The cytokine deficit
in milk after S. aureus inoculation in the lactating bovine mammary gland could contribute to the establishment of chronic mastitis. This result could help in the design of preventive or curative strategies against chronic mastitis.
INTRODUCTION
Top
Abstract
Introduction
Materials and Methods
Results
Discussion
References
(IL-1), IL-8, tumor necrosis factor-alpha
(TNF-
), granulocyte-macrophage colony-stimulating factor, and
gamma interferon, and the complement fragment C5a are known to be
important for the accumulation of leukocytes at sites of inflammation
(3, 10, 18, 38, 42). Cytokines can also enhance the
bactericidal activity of phagocytes (35, 43).
,
IL-1, IL-8, and C5a). To achieve this, experimental infections of
the bovine udder were carried out. E. coli-induced
inflammatory mediators in the bovine mammary gland have been the
subject of previous works, in contrast to S. aureus-induced
inflammatory mediators, which have never been studied. This research
related the moderate cell recruitment during S. aureus
infection to an apparent lack of production of the major
chemoattractant and inflammatory mediators in the luminal compartment
of the mammary gland, contrasting with the intense accumulation of
mediators in the case of E. coli infection. These results
contribute to a better understanding of subclinical, chronic infections
at an epithelial surface.
MATERIALS AND METHODS
Top
Abstract
Introduction
Materials and Methods
Results
Discussion
References
20°C) for subsequent cytokine
analysis. The skim milk was ultracentrifuged at 90,000 × g for 30 min, and the whey was harvested and stored frozen
(20°C) for subsequent BSA and cytokine analysis.
20°C) for subsequent haptoglobin analysis.
Assays. The SCC assays were performed with a Coulter Counter (Coultronics France S.A., Andilly, France). Differential cellular counts were performed under a microscope after May-Grünwald staining. Bacterial concentrations were obtained from cultures of appropriate dilutions of milk samples on sheep blood agar plates for 24 h at 37°C.
The concentration of BSA in milk samples was determined by the radial immunodiffusion technique (30). Haptoglobin in plasma was measured using a colorimetric method, and results were expressed as haptoglobin-binding capacity (Hb-BC mg/100 ml of plasma) (26). Whey samples were analyzed for TNF-, IL-1, and IL-8
concentrations, in addition to the complement fragment C5a
concentration. TNF- and C5a were quantified by enzyme-linked
immunosorbent assay (ELISA) as previously described (32,
33). Zymosan (2 mg/ml; Sigma Chemical Co., St. Louis, Mo.) was
used in vitro to activate, in the whey samples, the complement that was
not consumed in vivo; thereafter, C5a in both activated and
nonactivated whey samples was measured by ELISA. IL-1 was measured
by ELISA using commercial antibodies against ovine IL-1 (Serotec
Ltd., Oxford, England). The coating monoclonal antibody and the
detecting antiserum were diluted as suggested by the manufacturer. IL-8
was measured with a human IL-8 ELISA kit as described by the
manufacturer (R&D Systems, Minneapolis, Minn.). IL-8 in the milk cell
pellets was also measured using the same kit (27). Before
ELISA, frozen cells were suspended in saline buffer at a concentration
of 106 cells/ml and cells were lysed by two successive
cycles of freezing and thawing.
Levels of inflammatory mediators in milk whey are reported as
concentrations. No correction was made to account for changes in the
volume of milk within the gland at any particular time.
Statistical analysis. For each experiment (E. coli and S. aureus challenges), infected glands were compared to the same prechallenged glands in a paired t test. E. coli- and S. aureus-infected glands were compared in a two-sample t test. Data for bacterial concentrations and SCC were logarithmically transformed to maintain a normal distribution. Data are expressed as means ± standard errors of the means.
| |
RESULTS |
|---|
|
Top
Abstract
Introduction
Materials and Methods
Results
Discussion
References
|
|---|
Clinical signs. In the E. coli-challenged cows there was profound swelling of the infused quarters by 12 h, which increased in severity until 39 to 63 h, depending on the cow, and subsequently declined until quarters were normal by approximately 1 week. At the same times, the milk secretion was grossly abnormal, containing clots and from time to time blood. The S. aureus-infused glands showed no swelling, and there was no visible change in the milk appearance.
A systemic reaction occurred in association with the E. coli mastitic episode. Rectal temperatures increased from 38.3 ± 0.09°C to 41 ± 0.2°C at 16 h p.i. and were maximal at this time. After the S. aureus challenge, rectal temperatures did not increase (data not shown).Bacteria and somatic cells.
E. coli growth in the gland
was exponential until the 10th hour. The bacterial peak concentration
averaged 6.6 ± 0.3 log10 CFU/ml. The number of
bacteria decreased slowly from the 39th hour until the end of the
experiment (Fig. 1A). The SCC increased significantly (P < 0.015) from 5.07 ± 0.03 log10 cells/ml to 5.9 ± 0.2 log10
cells/ml at 12 h after E. coli infusion and reached a
maximum of 7.2 ± 0.02 log10 cells/ml at 72 h
p.i. (Fig. 1A). S. aureus growth in the udder was much lower
than E. coli growth and varied markedly from one cow to
another (Fig. 1B). The bacterial peak concentration averaged 4.4 ± 0.1 log10 CFU/ml at 11 days after challenge. The SCC
increased significantly (P < 0.04) from 5.01 ± 0.07 log10 cells/ml to 5.4 ± 0.1 log10
cells/ml at 24 h p.i. and reached a plateau at 5.9 ± 0.2 log10 cells/ml from day 3 to day 14 after challenge. SCC
kinetics were very different among the animals, and the SCC remained
significantly (P < 0.0004) lower than that observed in
E. coli-infected glands (Fig. 1B).
|
) and SCC (
) in milk samples from
quarters experimentally infected with E. coli (A) or
S. aureus (B). Data are expressed as means ± standard
errors of the means. *, significant difference (P < 0.05) compared with preinfection values.
BSA.
During the E. coli experimental mastitis, milk
BSA concentrations were significantly increased (P < 0.047) from the 12th hour p.i. (10.4 ± 3.6 mg/ml) compared
to the baseline concentrations (0.23 ± 0.02 mg/ml). The kinetics
of the BSA transudation (Fig. 2A) roughly
paralleled the somatic cell variations. These results were very
different from those obtained for the S. aureus-infected glands in which a slight but not significant increase in BSA
concentrations was observed (Fig. 2B).
|
Haptoglobin. Haptoglobin, an acute-phase protein that is not constitutive, was detected from the 8th hour p.i. in the sera of four E. coli-infected cows and from the 12th hour in the serum of the other cow. The mean of the maximal concentrations was high (119.6 ± 8.9 Hb-BC mg/100 ml of plasma), and concentrations remained elevated (P < 0.02) for all of the animals from the 16th hour to the 4th day (Fig. 2A). Haptoglobin was detected from 24 h p.i. in the sera of four S. aureus-infected cows and from 48 h p.i. in the sera of the other two cows (Fig. 2B). The increase was less pronounced than during E. coli infections, with a mean of the maximal values of 21.9 ± 6.3 Hb-BC mg/100 ml of plasma.
TNF-.
During the E. coli infection, TNF-
concentrations in whey increased dramatically between the 10th and the
39th hours p.i. The peak concentrations (14.1 ± 3.2 ng/ml) were
observed between the 14th and the 18th hours p.i. for all of the
animals. From 24 h p.i. on, the concentrations decreased rapidly
to a low level (Fig. 3). No TNF- was
detected in the whey obtained from the S. aureus-infected
animals.
|
), and IL-8 (IL-1.
Increases in IL-1 concentrations in whey from
E. coli-infected glands began slightly after increases in
TNF-, and maximal concentrations were reached later (Fig. 3). No
IL-1 was detected in whey obtained before challenge. In samples from
one cow, a very small amount of IL- was detected only at 48 h
p.i. In samples from the other five cows, peak levels ranged from 0.53 to 3.22 ng/ml. No IL-1 was detected in S. aureus-infected samples.
IL-8.
In the whey from the E. coli-infected cows,
IL-8 was detected from the 10th hour p.i. for one cow and from the 12th
hour p.i. for the others. The concentrations remained high (1.08 ± 0.1 ng/ml) during the first 2 days (P < 0.02) and
then decreased rapidly (Fig. 3). IL-8 was not detected in whey from
S. aureus-infected cows (the detection limit of the method
was 31 pg/ml). IL-8 in the milk cell pellets was also measured. Only
samples from one cow infected with E. coli were available
and analyzed. However, samples from the six S. aureus-infected cows were analyzed. High concentrations of IL-8
(20 pg/ml to 28.4 ng/ml, corresponding to 15 pg/106 cells
to 1.99 ng/106 cells) were detected in cells from the
E. coli-infused udder from the 16th hour p.i., so that most
IL-8 was cell associated at 40 h and after (Fig.
4). No IL-8 was detected in cells from S. aureus-infected glands.
|
C5a.
No C5a was detected in whey samples collected before
intramammary infusions. In whey of E. coli-infected animals,
C5a was detected from the 10th hour p.i. for four cows and from the
12th hour p.i. for the fifth cow. The kinetics was comparable to
kinetics of TNF-, but with a longer persistence (Fig.
5A). Some increases at sporadic points
were observed in three cows among the six that were infected with
S. aureus (Fig. 5B). The ability of milk to generate C5a was
also measured in the whey samples after addition of zymosan. The amount
of in vitro-generated C5a in E. coli infected animal whey
was huge, up to 100-fold the amount of the in vivo-generated C5a (Fig.
5C). In the S. aureus-infected animal whey, C5a was also
produced through complement activation. The quantities were not as high
as those found in E. coli-infected animal whey (the mean of
the maximal concentrations was 6.1 ± 1.9 ng/ml for S. aureus and 1.3 ± 0.4 µg/ml for E. coli during
the first 7 days p.i.). However, all of the samples contained
unconsumed complement during the studied inflammation time (Fig. 5D).
|
| |
DISCUSSION |
|---|
|
Top
Abstract
Introduction
Materials and Methods
Results
Discussion
References
|
|---|
The outcomes of the experimental infections performed in the present study were as expected on the basis of the current forms displayed by naturally occurring infections. Intramammary E. coli infusions provoked clinical mastitis with severe signs associated with a breakdown of the blood-milk barrier, as indicated by a coincident increase in BSA concentrations in milk. S. aureus infusions induced subclinical mastitis, which became chronic. The acute-phase response, which represents the host's reaction to the infection, involved the production and release of acute-phase proteins by the liver, demonstrating that a systemic inflammatory response developed. High levels of haptoglobin, the most reactive acute-phase protein in cattle (12), were measured in plasma of cows infected with E. coli during the first 4 days after challenge, in keeping with a previous report (34). Compared to E. coli mastitis, about 50-fold less haptoglobin was found in the plasma of S. aureus-infected cows, and haptoglobin was detected throughout the 21 days of the experiment, indicating that a systemic reaction developed and persisted, although with a much lower magnitude than in E. coli infections.
Following E. coli intramammary infusion, bacteria grew exponentially until the 10th hour p.i.; at that time, cells began to arrive in the udder and the growth was then controlled. The total eradication of bacteria occurred within 10 days after challenge without any therapeutic treatment. Compared to E. coli, S. aureus grew slower and reached a maximal concentration at 6 days p.i. Moreover, cells arrived later in the udder (between the 1st and the 4th days p.i. depending on the cow), and SCC kinetics were considerably heterogeneous among the cows. All of the challenged quarters became chronically infected. Our results support the hypothesis that the establishment of S. aureus chronic mastitis is the consequence of a low cell recruitment due to a quasiabsence of the major inflammatory mediators at the site of infection, at least in the milk compartment.
In response to intramammary E. coli infection, multiple
inflammatory mediators, including TNF-, interleukins, and C5a, are produced (38, 40). To our knowledge, no results are
available concerning S. aureus bovine mastitis. To better
understand staphylococcal mastitis, we compared the production of those
mediators in milk from E. coli- and S. aureus-infected quarters.
One of the major inflammatory cytokines that mediates the acute-phase
reaction is TNF-. The TNF- concentrations found following E. coli challenge in the present study are in accordance
with those in previous work where biologic tests were used to measure TNF- activity (37, 38, 40). In contrasting to the case for E. coli infection, no TNF- was found in the milk from
S. aureus-infected glands. The moderate reaction induced by
S. aureus could explain the fact that TNF- was not
detected. Indeed, intramammary infusions of a small amount (10 µg) of
E. coli endotoxin does not allow the measurement of TNF-
activity in milk (39), in contrast to the case for higher
doses (24, 37, 41). Nevertheless, the detection limit of the
method was 0.4 ng/ml. Since TNF- biological activity can be observed
at 0.01 ng/ml, it is not excluded that TNF- was present in those
samples at a low but active level.
Another major inflammatory cytokine is IL-8, a powerful chemoattractant for neutrophils (38). In accordance with previous work, no IL-8 was detected in any of the milk samples obtained before challenge (4). Following E. coli injection, we detected IL-8 earlier than Shuster et al. (38) (between the 14th and the 16th hours p.i., versus between the 24th and the 48th hours p.i.). We found the kinetics and concentrations of IL-8 to be very similar among the five challenged glands, in contrast to Shuster et al. (38), who described a heterogeneous production, with three of the eight infected glands not exhibiting obvious increases in IL-8.
No IL-8 was detected in milk from cows infected with S. aureus. In vitro, Barber and Yang (4) found that an
IL-8 neutrophil chemotactic activity exists in S. aureus
mastitic secretions. Therefore, it cannot be excluded that IL-8 was
present in the milk samples of S. aureus-infected cows at
concentrations of 
30 pg/ml (the detection limit of the ELISA kit). At
those low concentrations, the chemotactic activity of bovine IL-8 on
bovine neutrophils remains unknown, but strong chemotactic activity of
recombinant human IL-8 on bovine neutrophils was found at
concentrations of 50 pg/ml (28, 38). Since IL-8 has the
capability to link itself to cell membrane receptor or to be rapidly
internalized by cells (27), we also measured IL-8 in the
milk cell pellets. High levels of IL-8 were found in the cells from the
E. coli-infected cow during the inflammatory period,
suggesting that in previous studies, the quantities of IL-8 present in
inflammatory milk were underestimated (up to more than 100-fold in some
samples). In contrast to the case for the E. coli samples,
no IL-8 was detected in the S. aureus cell samples. This
result reinforced the results we obtained with the whey samples. The
fact that no TNF- or IL-1 was detected in whey samples of
S. aureus-infected cows could explain why IL-8 was not
detected either. Indeed, studies showed that IL-1 and TNF- stimulate
IL-8 secretion (25, 28). In contrast, TNF- and IL-1
must have enhanced IL-8 secretion in E. coli-infected glands.
The last inflammatory mediator we measured was the complement fragment C5a. The role of complement in the recruitment of leukocytes in the udder is still uncertain (9, 28, 38). In the milk of E. coli-infected cows, the presence of C5a was detected from the 12th hour p.i. and was concomitant with the cell arrival and IL-8 increase, so it was not possible to conclude if C5a represented the initial chemoattractive activity, as Shuster et al. suggested (38). In milk from S. aureus-infected animals, no C5a was detected, except sporadically in three animals. At those times, elevations of C5a concentrations were not correlated with increases in cell numbers in milk. Moreover, despite the absence of C5a, cell recruitment did occur following S. aureus infusion. Together, these results make clear that the cell recruitment in the udder was not dependent upon C5a chemoattractant activity.
The quasiabsence of C5a in milk from S. aureus-infected cows could be attributed to an absence of C5 activation or to a lack of C5 or any other complement components playing a role in the complement cascade before the C5a generation. To verify this hypothesis, unconsumed complement was activated by addition of zymosan, a complement activator, in infectious milk samples. The C5a eventually in vitro generated was then quantified. Some was detected from the 4th day to the 14th or the 28th day p.i., depending on the cow. These results showed that the absence of C5a in milk from S. aureus-infected cows was not due to a lack of complement in the udder. Therefore, S. aureus infection, under our experimental conditions, did not permit the activation of the complement. This can be attributed to an insufficient number of bacteria in milk or to an incapacity of S. aureus in activating the complement. Either case would contribute to the persistence of S. aureus, as C5a plays an important role in neutrophil activation (21).
The low cell recruitment during S. aureus infection appears to be the consequence of a lack of production of the chemoattractant or inflammatory mediators. The moderate numbers of S. aureus organisms in milk could explain this phenomenon by being below the threshold necessary for the triggering of an effective inflammatory response. Another explanation could be a repressive effect of S. aureus exerted on the expression of cytokines by the host cells, as has been observed with other bacteria (29, 36).
However, cell influx does exist after S. aureus intramammary infusions, and haptoglobin was detected in the plasma of infected cows, proving that there were local and systemic inflammatory reactions. Therefore, inflammatory mediators should have been synthesized at the site of infection, but none of the expected ones were detected in milk. S. aureus is known to adhere to the mammary epithelium, and several studies have demonstrated that epithelial cells can generate a variety of inflammatory mediators upon interaction with the bacteria (1, 13). Therefore, it could be conceivable that with S. aureus stimulation, the mammary epithelial cells could have secreted inflammatory cytokines directly in the interstitium. This could explain why there were neutrophil recruitment and a systemic inflammatory reaction without any cytokines detectable in the milk of the infected udder.
Further investigations, in particular on the contribution of epithelial cells to leukocyte recruitment, are necessary to understand those mechanisms. This could help in the development of strategies to prevent the installation of chronic mastitis in lactating cows.
| |
ACKNOWLEDGMENTS |
|---|
We are grateful to the dairy farm staff for assistance in
collecting milk and blood samples. We thank Thierry Cochard for assistance with bacteriological studies, Jacques Dufrenoy for technical
assistance, and Max Paape and Ted Elsasser (U.S. Department of
Agriculture, Beltsville, Md.) for providing the TNF- ELISA reagents.
| |
FOOTNOTES |
|---|
* Corresponding author. Mailing address: INRA, Laboratoire PII, Centre de Tours-Nouzilly, 37380 Nouzilly, France. Phone: (33) 2 47 42 76 33. Fax: (33) 2 47 42 77 79. E-mail: rainard{at}tours.inra.fr.
| |
REFERENCES |
|---|
|
Top
Abstract
Introduction
Materials and Methods
Results
Discussion
References
|
|---|
| 1. | Agace, W. W., S. R. Hedges, M. Ceska, and C. Svanborg. 1993. Interleukin-8 and the neutrophil response to mucosal gram-negative infection. J. Clin. Invest. 92:780-785. |
| 2. | Anderson, J. C. 1978. Absence of bacterial adherence in the establishment of experimental mastitis in mice. Vet. Pathol. 15:770-775[Abstract]. |
| 3. | Baggiolini, M., A. Walz, and S. L. Kunkel. 1989. Neutrophil-activating peptide-1/interleukin 8, a novel cytokine that activates neutrophils. J. Clin. Invest. 84:1045-1049. |
| 4. |
Barber, M. R., and T. J. Yang.
1998.
Chemotactic activities in nonmastitic and mastitic mammary secretions: presence of interleukin-8 in mastitic but not nonmastitic secretions.
Clin. Diagn. Lab. Immunol.
5:82-86 |
| 5. |
Bochner, B. S.,
F. W. Luscinskas,
J. Gimbrone,
W. Newman,
S. A. Sterbinsky,
A. C. Derse,
D. Klunk, and R. P. Schleimer.
1991.
Adhesion of human basophils, eosinophils, and neutrophils to interleukin 1-activated human vascular endothelial cells: contributions of endothelial cell adhesion molecules.
J. Exp. Med.
173:1553-1557 |
| 6. | Bramley, A. J. 1976. Variations in the susceptibility of lactating and non-lactating bovine udders to infection when infused with Escherichia coli. J. Dairy Res. 43:205-211[Medline]. |
| 7. | Carroll, E. J., R. Mueller, and L. Panico. 1982. Chemotactic factors for bovine leukocytes. Am. J. Vet. Res. 43:1661-1664[Medline]. |
| 8. | Christ, W. L., R. J. Harmon, and L. E. Newman. 1983. How much does mastitis cost? Udder Top. 6:6-9. |
| 9. | Colditz, I. G., and P. J. Maas. 1987. The inflammatory activity of activated complement in ovine and bovine mammary glands. Immunol. Cell Biol. 65:433-436. |
| 10. | Cybulsky, M. I., D. J. McComb, and H. Z. Movat. 1988. Neutrophil leukocyte emigration induced by endotoxin. Mediator roles of interleukin 1 and tumor necrosis factor alpha 1. J. Immunol. 140:3144-3149[Abstract]. |
| 11. |
Eberhart, R. J.,
R. P. Natzke, and F. H. S. Newbould.
1979.
Coliform mastitis a review.
J. Dairy Sci.
62:1-22.
|
| 12. | Eckersall, P. D., and J. G. Conner. 1988. Bovine and canine acute phase proteins. Vet. Res. Commun. 12:169-178[CrossRef][Medline]. |
| 13. |
Eckmann, L.,
M. F. Kagnoff, and J. Fierer.
1993.
Epithelial cells secrete the chemokine interleukin-8 in response to bacterial entry.
Infect. Immun.
61:4569-4574 |
| 14. |
Frost, A. J.
1975.
Selective adhesion of microorganisms to the ductular epithelium of the bovine mammary gland.
Infect. Immun.
12:1154-1156 |
| 15. | Goff, J. P., Y. Naito, M. E. J. Kehrli, P. Hayes, and M. Daley. 1992. Physiologic effects of administration of interleukin 1 beta in cows. Am. J. Vet. Res. 53:1983-1987[Medline]. |
| 16. | Gray, G. D., K. A. Knight, R. D. Nelson, and M. J. Herron. 1982. Chemotactic requirements of bovine leukocytes. Am. J. Vet. Res. 43:757-759[Medline]. |
| 17. | Gudding, R., J. S. McDonald, and N. F. Cheville. 1984. Pathogenesis of Staphylococcus aureus mastitis: bacteriologic, histologic, and ultrastructural pathologic findings. Am. J. Vet. Res. 45:2525-2531[Medline]. |
| 18. |
Hamilton, J. A.
1993.
Colony stimulating factors, cytokines and monocyte-macrophagessome controversies.
Immunol. Today.
14:18-24[CrossRef][Medline].
|
| 19. | Hill, A. W. 1994. Escherichia coli mastitis, p. 117-133. In C. L. Gyles (ed.), Escherichia coli in domestic animals and humans. Cab International, Wallingford, United Kingdom. |
| 20. | Hogan, J. S., K. L. Smith, and K. H. Hoblet. 1989. Field survey of clinical mastitis in low somatic cell count herds. J. Dairy Sci. 72:1547-1556. |
| 21. | Hopken, U. E., B. Lu, N. P. Gerard, and C. Gerard. 1996. The C5a chemoattractant receptor mediates mucosal defence to infection. Nature 383:86-89[CrossRef][Medline]. |
| 22. |
Huber, A. R.,
S. L. Kunkel,
R. F. Todd, and S. J. Weiss.
1991.
Regulation of transendothelial neutrophil migration by endogenous interleukin-8.
Science
254:99-102 |
| 23. |
Issekutz, A. C., and S. Bhimji.
1982.
Role for endotoxin in the leukocyte infiltration accompanying Escherichia coli inflammation.
Infect. Immun.
36:558-566 |
| 24. |
Lahti, P.,
E. M. Lilius,
M. J. Zurakowski, and M. J. Paape.
1994.
Tumor necrosis factor- (TNF-) responses in blood and mammary secretions after intramammary injection of endotoxin.
J. Dairy Sci.
11(Suppl. 1):255.
|
| 25. | Larsen, C. G., A. O. Anderson, J. J. Oppenheim, and K. Matsushima. 1989. Production of interleukin-8 by human dermal fibroblasts and keratinocytes in response to interleukin-1 or tumour necrosis factor. Immunology 68:31-36[Medline]. |
| 26. | Makimura, S., and N. Suzuki. 1982. Quantitative determination of bovine serum haptoglobin and its elevation in some inflammatory diseases. Nippon. Juigaku. Zasshi. 44:15-21[Medline]. |
| 27. | Marie, C., C. Fitting, C. Cheval, M. R. Losser, J. Carlet, D. Payen, K. Foster, and J. M. Cavaillon. 1997. Presence of high levels of leukocyte-associated interleukin-8 upon cell activation and in patients with sepsis syndrome. Infect. Immun. 65:865-871[Abstract]. |
| 28. | Persson, K., I. Larsson, and S. C. Hallen. 1993. Effects of certain inflammatory mediators on bovine neutrophil migration in vivo and in vitro. Vet. Immunol. Immunopathol. 37:99-112[CrossRef][Medline]. |
| 29. | Plitnick, L. M., J. A. Banas, D. M. Jelley-Gibbs, J. O'Neil, T. Christian, and S. P. Mudzinski. 1998. Inhibition of interleukin-2 by Gram-positive bacterium, Streptococcus mutans. Immunology 95:522-528[CrossRef][Medline]. |
| 30. | Poutrel, B., J. P. Caffin, and P. Rainard. 1983. Physiological and pathological factors influencing bovine serum albumin content of milk. J. Dairy Sci. 66:535-541. |
| 31. | Poutrel, B., and C. Lerondelle. 1978. Induced staphylococcal infections in the bovine mammary gland. Influence of the month of lactation and other factors related to the cow. Ann. Rech. Vet. 9:119-128[Medline]. |
| 32. | Rainard, P., and M. J. Paape. 1997. Sensitization of the bovine mammary gland to Escherichia coli endotoxin. Vet. Res. 28:231-238[Medline]. |
| 33. | Rainard, P., P. Sarradin, M. J. Paape, and B. Poutrel. 1998. Quantification of C5a/C5a(desArg) in bovine plasma, serum and milk. Vet. Res. 29:73-88[Medline]. |
| 34. | Salonen, M., J. Hirvonen, S. Pyorala, S. Sankari, and M. Sandholm. 1996. Quantitative determination of bovine serum haptoglobin in experimentally induced Escherichia coli mastitis. Res. Vet. Sci. 60:88-91[CrossRef][Medline]. |
| 35. | Sample, A. K., and C. J. Czuprynski. 1991. Priming and stimulation of bovine neutrophils by recombinant human interleukin-1 alpha and tumor necrosis factor alpha. J. Leukoc. Biol. 49:107-115[Abstract]. |
| 36. | Schesser, K., A. K. Spiik, J. M. Dukuzumuremyi, M. F. Neurath, S. Pettersson, and W. H. Wolf. 1998. The yopJ locus is required for Yersinia-mediated inhibition of NF-kappaB activation and cytokine expression: YopJ contains a eukaryotic SH2-like domain that is essential for its repressive activity. Mol. Microbiol. 28:1067-1079[CrossRef][Medline]. |
| 37. | Shuster, D. E., and M. E. J. Kehrli. 1995. Administration of recombinant human interleukin 1 receptor antagonist during endotoxin-induced mastitis in cows. Am. J. Vet. Res. 56:313-320[Medline]. |
| 38. | Shuster, D. E., M. E. J. Kehrli, P. Rainard, and M. Paape. 1997. Complement fragment C5a and inflammatory cytokines in neutrophil recruitment during intramammary infection with Escherichia coli. Infect. Immun. 65:3286-3292[Abstract]. |
| 39. | Shuster, D. E., M. E. J. Kehrli, and M. G. Stevens. 1993. Cytokine production during endotoxin-induced mastitis in lactating dairy cows. Am. J. Vet. Res. 54:80-85[Medline]. |
| 40. | Shuster, D. E., E. K. Lee, and M. E. J. Kehrli. 1996. Bacterial growth, inflammatory cytokine production, and neutrophil recruitment during coliform mastitis in cows within ten days after calving, compared with cows at midlactation. Am. J. Vet. Res. 57:1569-1575[Medline]. |
| 41. | Sordillo, L. M., and J. E. Peel. 1992. Effect of interferon-gamma on the production of tumor necrosis factor during acute Escherichia coli mastitis. J. Dairy Sci. 75:2119-2125[Abstract]. |
| 42. | Springer, T. A. 1994. Traffic signals for lymphocyte recirculation and leukocyte emigration: the multistep paradigm. Cell 76:301-314[CrossRef][Medline]. |
| 43. | Steinbeck, M. J., and J. A. Roth. 1989. Neutrophil activation by recombinant cytokines. Rev. Infect. Dis. 11:549-568[Medline]. |
| 44. |
Sutra, L., and B. Poutrel.
1994.
Virulence factors involved in the pathogenesis of bovine intramammary infections due to Staphylococcus aureus.
J. Med. Microbiol.
40:79-89 |
Clinical and Diagnostic Laboratory Immunology, March 2000, p. 161-167, Vol. 7, No. 2
1071-412X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
This article has been cited by other articles:
-
Griesbeck-Zilch, B., Osman, M., Kuhn, Ch., Schwerin, M., Bruckmaier, R. H., Pfaffl, M. W., Hammerle-Fickinger, A., Meyer, H. H. D., Wellnitz, O.
(2009). Analysis of key molecules of the innate immune system in mammary epithelial cells isolated from marker-assisted and conventionally selected cattle. J DAIRY SCI
92: 4621-4633
[Abstract] [Full Text] -
Rambeaud, M., Pighetti, G. M.
(2005). Impaired Neutrophil Migration Associated with Specific Bovine CXCR2 Genotypes. Infect. Immun.
73: 4955-4959
[Abstract] [Full Text] -
Chockalingam, A., Paape, M. J., Bannerman, D. D.
(2005). Increased Milk Levels of Transforming Growth Factor-{alpha}, {beta}1, and {beta}2 During Escherichia coli-Induced Mastitis. J DAIRY SCI
88: 1986-1993
[Abstract] [Full Text] -
Shamay, A., Homans, R., Fuerman, Y., Levin, I., Barash, H., Silanikove, N., Mabjeesh, S. J.
(2005). Expression of Albumin in Nonhepatic Tissues and its Synthesis by the Bovine Mammary Gland. J DAIRY SCI
88: 569-576
[Abstract] [Full Text] -
Vangroenweghe, F., Rainard, P., Paape, M., Duchateau, L., Burvenich, C.
(2004). Increase of Escherichia coli Inoculum Doses Induces Faster Innate Immune Response in Primiparous Cows. J DAIRY SCI
87: 4132-4144
[Abstract] [Full Text] -
Bannerman, D. D., Paape, M. J., Hare, W. R., Hope, J. C.
(2004). Characterization of the Bovine Innate Immune Response to Intramammary Infection with Klebsiella pneumoniae. J DAIRY SCI
87: 2420-2432
[Abstract] [Full Text] -
Bannerman, D. D., Paape, M. J., Lee, J.-W., Zhao, X., Hope, J. C., Rainard, P.
(2004). Escherichia coli and Staphylococcus aureus Elicit Differential Innate Immune Responses following Intramammary Infection. CVI
11: 463-472
[Abstract] [Full Text] -
Kuroishi, T., Komine, K.-i., Asai, K.-i., Kobayashi, J., Watanabe, K., Yamaguchi, T., Kamata, S.-i., Kumagai, K.
(2003). Inflammatory Responses of Bovine Polymorphonuclear Neutrophils Induced by Staphylococcal Enterotoxin C via Stimulation of Mononuclear Cells. CVI
10: 1011-1018
[Abstract] [Full Text]
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Copyright © 2009 by the American Society for Microbiology. For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»