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Clinical and Diagnostic Laboratory Immunology, September 2000, p. 817-822, Vol. 7, No. 5
Department of Pediatrics, University of
Göttingen, Göttingen, Germany,1 and
Division for Experimental Perinatal Pathology, Department
of Woman and Child Health, Karolinska Institute, Stockholm,
Sweden2
Received 15 December 1999/Returned for modification 16 February
2000/Accepted 5 July 2000
Connatal bacterial pneumonia is common in neonates. Animal studies
and initial clinical reports indicate that surfactant dysfunction is
involved in the pathophysiology of severe neonatal pneumonia. Since
respiratory distress syndrome and connatal pneumonia may be difficult
to differentiate in the first hours of life, neonates with respiratory
failure due to bacterial infections might receive surfactant. Under
such conditions surfactant components might be catabolized by bacteria
and promote bacterial growth. We therefore investigated the influence
of three modified natural (Curosurf, Alveofact, and Survanta) and two
synthetic (Exosurf and Pumactant) surfactant preparations on the growth
of bacteria frequently cultured from blood or tracheal aspirate fluid
in the first days of life. Group B streptococci (GBS),
Staphyloccocus aureus, and Escherichia coli
were incubated in a nutrient-free medium (normal saline) for 5 h
at 37°C, together with different surfactants at concentrations of 0, 1, 10, and 20 mg/ml. With the exception of E. coli,
incubation in saline alone led to a variable decrease in CFU. In the
presence of Alveofact, Exosurf, and Pumactant the decline in bacterial numbers was less marked than in saline alone. Curosurf was bactericidal in a dose-dependent fashion for GBS and had a strong negative impact on
the growth of a GBS subtype that lacked the polysaccharide capsule. In
contrast, Survanta (10 and 20 mg/ml) significantly promoted the growth
of E. coli, indicating that surfactant components may
actually serve as nutrients. We conclude that bacterial growth in
different surfactant preparations is influenced by microbial species
and the composition and dose of the surfactant. Further studies are
necessary to elucidate the mechanisms behind our findings and to
evaluate the effects of surfactant on bacterial growth in vivo.
Pulmonary surfactant is a complex
mixture of phospholipids and specific proteins that line the alveolar
surface of the lung. Its major function is to reduce surface tension,
thereby protecting the alveoli against collapse at the end of
expiration (8, 11, 39). In addition, the role of surfactant
in host defense against inhaled bacteria has been recognized over the
last several years (for a review, see reference 38).
Since the observation that surfactant deficiency in lungs of premature
newborns is responsible for the respiratory distress syndrome (RDS),
exogenous surfactant therapy has become an established treatment of RDS
(17). However, surfactant dysfunction has been described in
other pulmonary diseases. Surfactant inactivation probably plays a key
role in the pathophysiology of acute RDS due to pneumonia in neonates,
infants, and adults (32). The infection provokes an influx
of inflammatory cells with a resulting release of cytokines, enzymes,
and reactive oxygen metabolites. Disruption of the
epithelial-endothelial barrier leads to leakage of plasma proteins into
the airspaces with consequent inhibition of surfactant function. The
detrimental effects of plasma proteins on surfactant function can be
overcome in vitro by increasing the surfactant concentration (7,
15).
Group B streptococci (GBS), Staphylococcus aureus, and
Escherichia coli are responsible for most cases of
early-onset infections in the neonatal period (1, 29).
Neonates with severe respiratory failure due to pneumonia caused by
these organisms may therefore receive exogenous surfactant. It has been
speculated that surfactant given under such circumstances might serve
as a nutrient for bacteria and thereby promote microbial growth
(31). Only a few reports, with diverg results, have been
published concerning the direct influence of surfactant on bacterial
growth (3, 16, 19, 23). Either these studies evaluated the
effects of low phospholipid concentrations (<1 mg/ml) or the authors
did not specify the phospholipid concentration of the surfactant
material as crude extracts of bronchoalveolar lavage fluid from animal
sources were used. Only two studies have analyzed bacterial growth in
the presence of commercially available surfactant preparations
currently used for replacement therapy in newborns. Sherman et al.
(31) reported that complete natural surfactant derived from
human amniotic fluid or natural sheep bronchial lavage fluid promoted
the growth of GBS, whereas Exosurf, a synthetic surfactant containing
two alcohols as spreading agents, was bactericidal. Intermediate
effects were observed for modified natural surfactants derived from
bovine, porcine, or calf lungs. Neumeister et al. (27)
observed that the modified bovine surfactant Survanta significantly
promoted the growth of E. coli. However, these observations
were either limited to one bacterial strain (31) and/or one
phospholipid concentration (27, 31).
The purpose of this study was to examine the effects of different
phospholipid concentrations of three modified natural (Curosurf, Alveofact, and Survanta) and two synthetic (Exosurf and Pumactant) surfactant preparations on the in vitro proliferation of GBS, S. aureus, and E. coli.
Bacterial strains.
By repeated gradient centrifugation
(9), we produced a low-density and a high-density phase
variant (LD and HD, respectively) from the GBS strain 090 Ia Colindale.
The strain was a gift from Stellan Håkansson, University of Umeå,
Umeå, Sweden, and was originally isolated from a neonate with
early-onset septicemia. We also studied two GBS wild-type strains
(Lancefield serotypes Ib and III) isolated from two neonates with GBS
septicemia. The serotypes Ia, Ib, and III account for most neonatal
infections, whereas subtype II is more commonly observed in
GBS-infected adults. The GBS LD subpopulation is abundantly
encapsulated, whereas GBS HD lacks a polysaccharide capsule.
1071-412X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Influence of Modified Natural or Synthetic
Surfactant Preparations on Growth of Bacteria Causing Infections
in the Neonatal Period
ABSTRACT
Top
Abstract
Introduction
Materials and Methods
Results
Discussion
References
INTRODUCTION
Top
Abstract
Introduction
Materials and Methods
Results
Discussion
References
MATERIALS AND METHODS
Top
Abstract
Introduction
Materials and Methods
Results
Discussion
References
70°C in 1-ml aliquots of nutrient broth
(Standard I; Merck, Darmstadt, Germany) composed of the following
(concentrations are in milligrams per milliliter): peptone, 15.0;
sodium chloride, 6.0; yeast extract, 3.0; and D(+)-glucose, 1.0. Before use bacteria were transferred to 11.5 ml of broth and
cultured for 16 h at 37°C. Working cultures were made by growing the bacteria to the mid-logarithmic phase. For this, the starter culture was diluted 1:7 with fresh prewarmed broth and incubated for
3 h at 37°C. Subsequently, the bacteria were harvested by centrifugation at 1,800 × g for 10 min, washed twice
with sterile isotonic saline, and resuspended in saline at a final
concentration of 8 × 108 CFU/ml. Bacterial
suspensions were adjusted to the desired concentrations by
determination of the optical density at 595 nm (Ultrospec III; Pharmacia Biotech, Freiburg, Germany) with reference to standard curves
established by plating 10-fold dilutions of the suspension on Columbia
agar plates with 5% sheep blood (Oxoid, Wesel, Germany).
Surfactant preparations. Curosurf (batch no. 96/0052; Chiesi Farmaceutici, Parma, Italy) is produced from minced pig lungs and consists of 99% phospholipids and 1% surfactant proteins. Alveofact (SF-RI 1, July 1997; Dr. Karl Thomae, Ltd., Biberach, Germany), a compound obtained from bovine lung lavage, is composed of 90% phospholipids, about 1% proteins, 3% cholesterol, 0.5% free fatty acids, and other components, including triglycerides. Survanta (batch no. 95-896Z7; Abbott, Ltd., Wiesbaden, Germany) is prepared by lipid extraction of minced bovine lungs and contains approximately 84% phospholipids, 1% proteins, and 6% free fatty acids. To this preparation dipalmitoylphosphatidylcholine (DPPC), palmitic acid, and tripalmitin are added to standardize the composition. Exosurf (batch no. T4798A; Wellcome, Burgwedel, Germany), a totally synthetic, protein-free surfactant, is composed of DPPC (~84%), cetyl alcohol, and tyloxapol. Pumactant (ALEC [artificial lung expanding compound] batch no. 82; Britannia Pharmaceuticals, Redhill, Surrey, United Kingdom) is an artificial, protein-free compound composed to 100% of a mixture of DPPC and phosphatidylglycerol at a weight ratio of 7:3.
Table 1 demonstrates the relative differences in composition of each of the commercially available surfactant preparations in comparison with human natural surfactant obtained from amniotic fluid. Human surfactant contains a small proportion of carbohydrates, antioxidants, and antibacterial peptides. Such components (e.g., the antibacterial peptide prophenin [36] detected in Curosurf) or platelet-activating factor (detected in Survanta and Curosurf [26]) are contained in trace amounts in modified natural surfactants.
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Bacterial growth in surfactant.
To determine the effects of
different surfactant preparations on bacterial growth, we incubated a
bacterial suspension containing 7 × 107 CFU/ml with
different concentrations of surfactant (1, 10, and 20 mg/ml) or without
surfactant (control) in saline at a final volume of 1 ml. Saline was
used to mimic a nutrient-free medium that would allow the bacteria to
use surfactant components as nutrients. Due to carbon dioxide exchange
the pH in the alveolar lining fluid is as low as 6.9 and the potassium
concentration is higher than in serum (28). However,
adjustment of the pH of our samples to 6.9 with a buffer, or adapting
the electrolyte content to that of alveolar fluid (sodium, 135 mmol/liter; chloride, 103 mmol/liter; potassium, 7.3 mmol/liter;
calcium, 3.2 mmol/liter) had no effect on the survival of GBS LD in
comparison with incubation in normal saline alone (Table
2). Since the metabolic rate of bacteria
incubated in a nutrient-free medium is low, the pH of GBS suspended in
saline was nearly constant throughout the 5-h experiment. Since the
surfactant phospholipids are suspended in saline the pH of Curosurf (pH
5.7) is virtually identical to that of saline (pH 5.8) so that the
addition of different amounts of Curosurf did not alter pH of the
suspension.
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Statistical analysis.
All data represent the mean and
standard deviation (SD) of six repeated experiments. For analysis, a
logarithmic transformation of the data (log10 CFU/ml) was
calculated, since bacterial growth follows a logarithmic growth curve.
Data points in figures were calculated as follows: the
log10 CFU/ml at time zero was subtracted from that at
5 h, so that a positive log10 difference [
(5
h, 0 h) log10 CFU/ml] indicates the bacterial
growth, and a negative log10 difference represents a
decrease in the number of bacteria. The statistical significance
between the growth rate of bacteria incubated with surfactant versus
the saline control group was tested by Dunnett's multiple comparison
test for analysis of variance using GraphPad software (GraphPad
Software, Inc., San Diego, Calif.). Statistical significance was
accepted at P values of <0.05.
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RESULTS |
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Top
Abstract
Introduction
Materials and Methods
Results
Discussion
References
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Effects of modified natural surfactants on bacterial survival. (i)
Curosurf.
Curosurf in normal saline reduced the growth of both GBS
with (LD) or without (HD) polysaccharide capsule (Fig.
1A). The number of viable HD GBS after
5 h of incubation was significantly decreased at Curosurf
concentrations of 10 and 20 mg/ml compared to saline controls without
Curosurf. No such decrease in bacterial numbers was observed for
S. aureus or E. coli. Compared to S. aureus incubated in saline, the numbers of CFU per milliliter were
slightly higher in solutions containing surfactant (Fig. 1A), but there
was no increase in bacterial numbers compared to the number of CFU
inoculated into the medium at the beginning of the experiments (0 h).
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(ii) Alveofact. In the presence of Alveofact, all gram-positive bacteria demonstrated increased viability compared to GBS HD, GBS LD, or S. aureus incubated in saline alone (Fig. 1B). In contrast to the findings with Curosurf, no inhibitory effect was observed on the growth of both phase variants of GBS. No differences were observed between the effects of Curosurf and Alveofact when the surfactants were incubated with S. aureus. The survival of E. coli was not influenced by Alveofact (Fig. 1B).
(iii) Survanta.
The addition of different concentrations of
Survanta to GBS LD did not alter bacterial survival over the 5-h
period, whereas Survanta seemed to protect GBS HD and S. aureus against the bactericidal effect of 5 h of incubation
in saline alone (Fig. 1C). Unlike all other tested surfactant
preparations, Survanta significantly promoted the growth of E. coli. At phospholipid doses of 
10 mg/ml, the numbers of CFU per
milliliter were increased 4.5 times compared to the bacterial count at
the beginning of the experiments (0 h).
Effects of synthetic surfactants on bacterial survival: Exosurf and Pumactant. Incubation of bacteria in Exosurf (Fig. 1D) or Pumactant (Fig. 1E) resulted in a similar growth pattern. No effects were observed on GBS LD and E. coli. However, compared to the incubation in saline alone, both surfactants protected GBS HD and S. aureus from the negative impacts of incubation on cell viability in a nutrient-free medium.
Bacterial survival of different GBS subtypes in the presence of
Curosurf.
Figure 2 shows the
survival of different GBS subtypes incubated in saline or in saline
containing 1, 10, or 20 mg of Curosurf per ml. The nonencapsulated HD
variant of GBS was most sensitive to the negative impact of surfactant
on survival. At Curosurf concentrations of 10 or 20 mg/ml, <1% of the
initial number of bacteria were viable after 5 h of incubation. In
contrast, the abundantly encapsulated strain GBS LD survived 5 h
of incubation in saline without a significant decrease in the number of
CFU. The effects observed following incubation of GBS LD with 20 mg of
Curosurf per ml were rather moderate compared to incubation of GBS HD
and the GBS wild-type strains with the same surfactant dose.
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DISCUSSION |
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Top
Abstract
Introduction
Materials and Methods
Results
Discussion
References
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We evaluated bacterial proliferation under the influence of different natural and synthetic surfactant preparations that are in clinical use in Europe and/or the United States. For our studies we chose GBS, S. aureus, and E. coli since more than 75% of cases of early-onset neonatal septicemia are caused by these organisms. Connatal infections often trigger premature birth and might be followed by respiratory failure within the first hours of life. Studies of surfactant treatment in infants with "idiopathic" RDS reveal that up to 20% of surfactant-treated neonates demonstrate signs of infection within the first days of life (for a review, see reference 12). All of the surfactant preparations investigated in this study have therefore been used in newborns with respiratory failure due to pneumonia.
Recommended doses for surfactant replacement therapy vary between 50 and 200 mg/kg of body weight for the initial treatment of babies with RDS. It has been recognized that doses of 300 mg of surfactant per kg (body weight) may be needed to overcome surfactant inhibition in pneumonia (35) or meconium aspiration syndrome (6). Such high doses would, even in babies devoid of endogenous surfactant, probably result in phospholipid concentrations well above 10 mg/ml in the alveolar lining layer, at least after resorption of fetal lung liquid (21). We speculate, on the basis of our present findings, that the surfactant layer on the alveolar surface might be an important part of the pulmonary defense system.
We found that Curosurf inhibited survival of GBS in saline in a dose-related fashion. For S. aureus, incubation in saline alone had a bactericidal effect. When Curosurf was added S. aureus was protected to some extent against the negative impact of the nutrient-free medium on microbial viability. In contrast, the viability of E. coli was unaffected by Curosurf, as well as by Alveofact, Exosurf, and Pumactant. These results probably reflect variations in the metabolic demands of different bacteria. In our in vitro assay system the bacteria were incubated in sterile saline, a nutrient-free medium. However, our own results of incubation of GBS and Curosurf in a culture medium containing glucose and protein (Table 2), as well as similar studies by Neumeister et al. (27), demonstrated that incubation of bacteria in nutrient-rich growth-promoting broth might mask the effects of surfactant that were observed when saline alone was used as a medium. Under normal physiological circumstances the alveolar lining fluid may be considered to be relatively poor in nutrient content. However, in the course of pneumonia and mechanical ventilation, serum components, including albumin and glucose, may leak into the bronchoalveolar space and increase the amount of nutrients available for bacterial proliferation.
Both the nonencapsulated GBS HD and S. aureus showed a slight decline in CFU during the 5-h incubation in sterile saline alone. GBS HD, the nonencapsulated phase variant, demonstrated a strong decline in viability when incubated with Curosurf, whereas GBS LD was clearly less susceptible under similar conditions, probably protected by the polysaccharide capsule. The capsule is an important virulence factor in GBS infections, and wild-type strains often contain a mixture of both encapsulated and nonencapsulated bacteria (9). These findings demonstrate that different subtypes of one bacterial species might differ in their interactions with surfactant. When we tested different clinical isolates from infants with GBS septicemia, the observed variation was small compared to the differences between different bacterial species. A similar observation was made by Neumeister et al. (27), who compared the influence of surfactant on different reference strains and several clinical isolates of GBS, S. aureus, and E. coli.
Several years ago, Coonrod and Yoneda (3) demonstrated that the surfactant fraction of rat alveolar lining material caused lysis of Streptococcus pneumoniae and several other gram-positive bacteria (Streptococcus viridans, Streptococcus pyogenes, and Streptoccoccus bovis). These authors speculated that the observed bactericidal effect was due to free fatty acids contained in the lung lavage preparation (5). More recently, Brogden et al. (2) described an anionic bactericidal peptide in bovine pulmonary surfactant, and prophenin-1, an antibacterial peptide that might be associated with surfactant lipids, has been isolated from porcine leukocytes (10). This antibacterial peptide has also been found in Curosurf, a surfactant extracted from porcine lung homogenate (36). Part of the observed effects may thus be due to direct negative effects of these bactericidal peptides on the bacterial cell wall. The polarity of these peptides seems to be most important for their antibacterial activity. It has been shown that changes in, for example, the sodium, zinc, calcium, or phosphorus content of the incubation medium can modify the in vitro bactericidal activity of such peptides (2, 10, 36).
We found that all of the investigated surfactant preparations protected S. aureus from the negative effects of saline on bacterial growth. This might indicate that staphylococci can catabolize surfactant lipids to some extent. The production and release of phospholipases by S. aureus has been described (24). LaForce et al. (22) reported increased growth of S. aureus after incubation with complete natural rabbit surfactant. Apparently, the bacteria can use surfactant components as nutrients. Natural surfactant isolated by lung lavage and subsequent sucrose gradient centrifugation contains a small proportion of carbohydrates (<1%) and ca. 10% proteins, including the specific surfactant-associated proteins (SP-A, SP-B, SP-C, and SP-D) (18). The hydrophilic proteins SP-A and SP-D are potent stimulators of macrophage function and are generally believed to serve as important components of the pulmonary host defense system against invading microorganisms (34). However, these proteins are removed by extraction with organic solvents and therefore absent in all of the industrially produced modified natural surfactants examined in the present study. SP-B, present in small amounts in all modified natural surfactants, may in itself have a bacteriostatic effect (see below).
The relative resistance of gram-negative E. coli to each of the investigated surfactants may reflect the failure of the surfactant molecules to penetrate the lipopolysaccharide layer. In fact, incubation of E. coli with Survanta significantly promoted bacterial growth. This has also been reported by other investigators (27). Recently, it has been shown that proliferation of E. coli is inhibited by mature human pulmonary SP-B or, more specifically, by residues 12 to 34 of SP-B (20). The reason for the observed proliferation of E. coli is unclear, but Survanta contains relatively little SP-B (25, 30) and, in contrast to the other modified natural surfactants examined, it is enriched with artificial lipids. Increased growth of E. coli has also been reported after exposure to a crude surfactant preparation obtained from dog lungs (16). In the present study, synthetic surfactants containing lipids only (Pumactant) or lipids plus spreading agents (Exosurf) had no effect on the proliferation of E. coli. Although differences in surfactant composition might explain some of these seemingly conflicting results, species differences may also play a role. For example, the clearing rate of inhaled pneumococci varies between different animals (4).
Our finding that some surfactant preparations may enhance bacterial survival or even promote bacterial proliferation (as observed for Survanta and E. coli) is certainly alarming and should be further studied in animal experiments. So far most studies on surfactant for treatment of inflammatory lung disease have focused on gas exchange. Song et al. demonstrated improved lung function in rats with E. coli pneumonia treated with Curosurf (33). Unfortunately, no attempts were made to examine bacterial growth in that study. Interestingly, the present in vitro data obtained with Curosurf and GBS are in keeping with our previous observations made with GBS-infected newborn rabbits, showing mitigation of bacterial proliferation in lung homogenate following treatment with this particular surfactant preparation (13).
Clinical and radiological signs do not differentiate with certainty between pneumonia and RDS in the first hours of life. Since we and others have observed that some surfactant preparations might promote bacterial growth, infants with severe respiratory failure treated with surfactant should receive antibiotic therapy until infection can be ruled out by culture and laboratory findings.
We conclude that bacterial growth in the presence of surfactant depends on the bacterial species and the origin and concentration of the applied surfactant preparation. Except for cultures of E. coli in Survanta, most surfactants do not seem to promote bacterial growth. However, E. coli is now rarely isolated from blood cultures or tracheal aspirate fluid in the neonatal period. Curosurf significantly diminished the proliferation of GBS, the organism that accounts for most cases of early-onset septicemia. Initial clinical observations give us no reason to believe that treatment with surfactant should have serious adverse effects in neonates with connatal pneumonia (14) but, clearly, further in vivo studies are necessary to clarify the relevance of the effects observed here. Even if exogenous surfactant obtained from animal lungs influences bacterial growth in vitro, the effects of exogenous phospholipids on the microbiology of the human lung remain unclear. Careful follow-up of babies with bacterial infections treated with surfactant therefore seems mandatory.
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ACKNOWLEDGMENTS |
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We thank Docent Connie Jarstrand, Department of Immunology, Microbiology, Pathology, and Infectious Diseases, Karolinska Institute, Huddinge Hospital, Stockholm, Sweden, for technical advice and critical discussion.
This study was supported by the Deutsche Forschungsgemeinschaft (DFG He 2072/2-2), the Swedish Medical Research Council (project 3351), and a collaborative project of the German Academic Exchange Service and the Swedish Institute (313/S-PPP).
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FOOTNOTES |
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* Corresponding author. Mailing address: Department of Pediatrics, University of Göttingen, Robert-Koch Str. 40, D-37075 Göttingen, Germany. Phone: 49-551-396210/396222. Fax: 49-551-396231. E-mail: eherting{at}med.uni-goettingen.de.
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REFERENCES |
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Abstract
Introduction
Materials and Methods
Results
Discussion
References
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| 1. | Baker, C. J., and M. S. Edwards. 1995. Group B streptococcal infections, p. 980-1054. In J. S. Remington, and J. O. Klein (ed.), Infectious diseases of the fetus and newborn infant, 4th ed. The W. B. Saunders Co., Philadelphia, Pa. |
| 2. |
Brogden, K. A.,
A. J. De Lucca,
J. Bland, and S. Elliot.
1996.
Isolation of an bovine pulmonary surfactant-associated anionic peptide bactericidal for Pasteurella haemolytica.
Proc. Natl. Acad. Sci. USA
93:412-416 |
| 3. | Coonrod, J. D., and K. Yoneda. 1983. Detection and partial characterization of antibacterial factors in alveolar lining material of rats. J. Clin. Investig. 71:129-141. |
| 4. | Coonrod, J. D., R. Varble, and M. C. Jarrells. 1990. Species variation in the mechanism of killing inhaled pneumococci. J. Lab. Clin. Med. 116:354-362[Medline]. |
| 5. | Coonrod, J., R. L. Lester, and L. C. Hsu. 1984. Characterization of the extracellular bactericidal factors of rat alveolar lining material. J. Clin. Investig. 74:1269-1279. |
| 6. |
Findlay, R. D.,
H. W. Taeusch, and F. J. Walther.
1996.
Surfactant replacement therapy for meconium aspiration syndrome.
Pediatrics
97:48-52 |
| 7. |
Fuchimukai, T.,
T. Fujiwara,
A. Takahashi, and G. Enhorning.
1987.
Artificial pulmonary surfactant inhibited by proteins.
J. Appl. Physiol.
62:429-437 |
| 8. | Goerke, J. 1998. Pulmonary surfactant: functions and molecular composition, p. 79-89. In L. M. G. van Golde (ed.), Pulmonary surfactant: from surface chemistry via biochemistry to clinical practice. BBA-Molecular Basis of Disease Section. Elsevier Science Publishers, Amsterdam, The Netherlands. |
| 9. | Håkansson, S., M. Granlund-Edstedt, M. Sellin, and S. E. Holm. 1990. Demonstration and characterization of buoyant-density subpopulations of group B streptococcus type III. J. Infect. Dis. 161:741-746[Medline]. |
| 10. | Harwig, S. S. L., V. N. Kokryakov, K. M. Swiderek, G. M. Aleshina, C. Zhao, and R. I. Lehrer. 1995. Prophenin-1, an exceptionally proline-rich antimicrobial peptide from porcine leukocytes. FEBS Lett. 362:65-69[CrossRef][Medline]. |
| 11. | Hawgood, S., and J. A. Clements. 1990. Pulmonary surfactant and its apoproteins. J. Clin. Investig. 86:1-6. |
| 12. | Herting, E. 1998. Surfactant therapy for neonatal pneumonia and for meconium aspiration syndrome, p. 124-132. In R. R. Wauer (ed.), Surfactant therapy: basic principles, diagnosis, therapy. Thieme, Stuttgart, Germany. |
| 13. | Herting, E., C. Jarstrand, O. Rasool, T. Curstedt, B. Sun, and B. Robertson. 1994. Experimental neonatal group B streptococcal pneumonia: effect of a modified porcine surfactant on bacterial proliferation in ventilated near-term rabbits. Pediatr. Res. 36:784-791[Medline]. |
| 14. | Herting, E., O. Gefeller, M. Land, L. van Sonderen, K. Harms, B. Robertson, and members of the Collaborative European Multicenter Study Group. Surfactant treatment of neonates with respiratory failure and group B streptococcal infection. Pediatrics, in press. |
| 15. | Holm, B. A., G. Enhorning, and R. H. Notter. 1988. A biophysical mechanism by which plasma proteins inhibit lung surfactant activity. Chem. Phys. Lipids 49:49-55[CrossRef][Medline]. |
| 16. | Jalowayski, A. A., and S. T. Giammona. 1972. The interaction of bacteria with pulmonary surfactant. Am. Rev. Respir. Dis. 105:236-241[Medline]. |
| 17. |
Jobe, A. H.
1993.
Pulmonary surfactant therapy.
N. Engl. J. Med.
328:861-868 |
| 18. | Johansson, J. 1994. The proteins of the surfactant system. Eur. Respir. J. 7:372-391[Abstract]. |
| 19. | Jonsson, S., D. Musher, A. Goree, and E. C. Lawrence. 1986. Human alveolar lining material and antibacterial defenses. Am. Rev. Respir. Dis. 133:136-140[Medline]. |
| 20. | Kaser, M. R., and G. G. Skouteris. 1997. Inhibition of bacterial growth by synthetic SP-B1-78 peptides. Peptides 18:1441-1444[CrossRef][Medline]. |
| 21. | Kobayashi, T., A. Shido, K. Nitta, S. Inui, M. Ganzuka, and B. Robertson. 1990. The critical concentration of surfactant in fetal lung liquid at birth. Respir. Physiol. 80:181-192[CrossRef][Medline]. |
| 22. | LaForce, F. M. 1976. Effect of alveolar lining material on phagocytic and bactericidal activity of lung macrophages against Staphylococcus aureus. J. Lab. Clin. Med. 88:691-699[Medline]. |
| 23. | LaForce, F. M., and D. S. Boose. 1981. Sublethal damage of Escherichia coli by lung lavage. Am. Rev. Respir. Dis. 124:733-737[Medline]. |
| 24. | Matos, J. E., R. J. Harmon, and B. E. Langlois. 1995. Lecithinase reaction of Staphylococcus aureus strains of different origin on Baird-Parker medium. Lett. Appl. Microbiol. 21:334-335[Medline]. |
| 25. | Mizuno, K., M. Ikegami, C. M. Chen, T. Ueda, and A. H. Jobe. 1995. Surfactant protein-B supplementation improves in vivo function of a modified natural surfactant. Pediatr. Res. 37:271-276[Medline]. |
| 26. | Moya, F. R., D. R. Hoffman, B. Zhao, and J. M. Johnston. 1993. Platelet activating factor in surfactant preparations. Lancet 345:858-860[CrossRef]. |
| 27. | Neumeister, B., S. Woerndle, and P. Bartmann. 1996. Effects of different surfactant preparations on bacterial growth in vitro. Biol. Neonate 70:128-134[Medline]. |
| 28. |
Nielsson, D. W.
1986.
Electrolyte composition of pulmonary alveolar subphase in anesthetized rabbits.
J. Appl. Physiol.
60:972-979 |
| 29. | Philip, A. G. S. 1994. The changing face of neonatal infection: experience at a regional medical center. Pediatr. Infect. Dis. J. 13:1098-1102[Medline]. |
| 30. | Seeger, W., C. Grube, A. Günther, and R. Schmidt. 1993. Surfactant inhibition by plasma proteins: differential sensitivity of various surfactant preparations. Eur. Respir. J. 6:971-977[Abstract]. |
| 31. | Sherman, M. P., L. A. Campbell, T. A. Merritt, W. A. Long, J. H. Gunkel, T. Curstedt, and B. Robertson. 1994. Effect of different surfactants on pulmonary group B streptococcal infection in premature rabbits. J. Pediatr. 125:939-947[CrossRef][Medline]. |
| 32. |
Somerson, N. L.,
S. B. Kontras,
J. D. Pollack, and H. S. Weiss.
1971.
Pulmonary compliance: alteration during infection.
Science
171:66-68 |
| 33. | Song, G. W., B. Robertson, T. Curstedt, X. Z. Gan, and W. X. Huang. 1996. Surfactant treatment in experimental Escherichia coli pneumonia. Acta Anaesthesiol. Scand. 40:1152-1159. |
| 34. | Van Golde, L. M. G. 1995. Potential role of surfactant proteins A and D in innate lung defense against pathogens. Biol. Neonate 67(Suppl. 1):2-17. |
| 35. | Walmrath, D., A. Günther, H. A. Ghofrani, R. Schermuly, T. Schneider, F. Grimminger, and W. Seeger. 1996. Bronchoscopic surfactant administration in patients with severe adult respiratory distress syndrome and sepsis. Am. J. Respir. Crit. Care Med. 154:57-62[Abstract]. |
| 36. | Wang, Y., W. J. Griffiths, T. Curstedt, and J. Johansson. 1999. Porcine pulmonary surfactant preparations contain the antibacterial peptide prophenin and a C-terminal 18-residue fragment thereof. FEBS Lett. 460:257-262[CrossRef][Medline]. |
| 37. | Wauer, R. 1998. Respiratory distress syndrome, p. 2-19. In R. R. Wauer (ed.), Surfactant therapy: basic principles, diagnosis, therapy. Thieme, Stuttgart, Germany. |
| 38. |
Wright, J. R.
1997.
Immunomodulatory functions of surfactant.
Physiol. Rev.
77:931-962 |
| 39. | Wright, J. R., and J. A. Clements. 1987. Metabolism and turnover of lung surfactant. Am. Rev. Respir. Dis. 135:426-444[Medline]. |
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