Previous Article | Next Article ![]()
Clinical and Diagnostic Laboratory Immunology, January 1998, p. 58-64, Vol. 5, No. 1
Departments of
Medicine2 and
Microbiology and
Immunology,1 Albert Einstein College of
Medicine, Bronx, New York 10461
Received 7 July 1997/Returned for modification 24 September
1997/Accepted 21 October 1997
The human immunoglobulin M (IgM) monoclonal antibody (MAb) 2E9
binds the glucuronoxylomannan (GXM) of Cryptococcus
neoformans serotypes A, B, and D. This study was undertaken to
determine the opsonic efficacy of 2E9 and its ability to promote the
antifungal activity of human polymorphonuclear neutrophils (PMNs)
against C. neoformans. We incubated purified PMNs with
fluorescein isothiocyanate-labeled C. neoformans cells that
were treated with the GXM IgM 2E9, IgM antibodies that do not bind GXM,
and rabbit and human factor-B-deficient serum as complement sources.
PMN-associated C. neoformans cells fluoresced and were
detected with a fluorescence-activated cell sorter. The amount of
phagocytosis was defined as the percent fluorescing PMNs, which was
37% for yeast cells opsonized with 2E9 plus rabbit serum and 57% for
yeast cells opsonized with 2E9 plus factor-B-deficient serum.
Phagocytosis was significantly greater for yeast cells that were
treated with 2E9 plus a complement source than for yeast cells treated
with the complement sources alone or treated with the control IgMs
alone or with the complement sources. Fluorescence quenching and light
and electron microscopy of the phagocytosis mixtures revealed that
2E9-opsonized yeast cells were internalized by PMNs. Maximal inhibition
of C. neoformans growth occurred when PMNs were cocultured
with yeast cells that were opsonized with 2E9 plus a complement source.
Our data demonstrate that the human GXM IgM 2E9 can mediate PMN
phagocytosis and C. neoformans growth inhibition in vitro.
These findings strongly suggest that antibody-mediated deposition of
complement components on the cryptococcal capsule can augment PMN
complement receptor-mediated antifungal activity. Antibody activation
of complement-mediated effector cell antifungal mechanisms may play a
role in host defense against cryptococcosis and represents a goal for
the use of MAbs to treat or prevent human C. neoformans
infections.
1071-412X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
Antifungal Activity of a Human
Antiglucuronoxylomannan Antibody
*
Corresponding author. Mailing address: Division of
Infectious Disease, Room 402 Forchheimer Building, 1300 Morris Park
Ave., Bronx, NY 10461. Phone: (718) 430-2372. Fax: (718) 430-8968. E-mail: pirofski{at}aecom.yu.edu.
This article has been cited by other articles:
| Antimicrob. Agents Chemother. | Clin. Microbiol. Rev. | Infect. Immun. |
|---|---|---|
| J. Clin. Microbiol. | J. Virol. | ALL ASM JOURNALS |