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Infection and Immunity, February 2002, p. 517-527, Vol. 70, No. 2
0019-9567/01/$04.00+0 DOI: 10.1128/IAI.70.2.517-527.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.
and Herbert L. Mathews*
Department of Microbiology and Immunology, Loyola University of Chicago, Maywood, Illinois 60153
Received 25 June 2001/ Returned for modification 23 July 2001/ Accepted 10 October 2001
Adherence of lymphocytes to the fungus is the first step in the direct lymphocyte-mediated antifungal effect against Candida albicans. In this study we identified macrophage-1 antigen (Mac-1) (CD11b/CD18,
M/ß2) as the lymphocyte surface structure responsible for the adhesion of activated lymphocytes to the hyphal form of the fungus. Antibodies specific for epitopes of the
-subunit (CD11b) and the ß2-subunit (CD18) of Mac-1 were shown to completely eliminate lymphocyte adhesion to C. albicans hyphae. Lymphocyte adhesion to C. albicans was also inhibited significantly by known ligands of Mac-1, including the extracellular matrix proteins laminin and fibrinogen, as well as engineered peptides containing arginine-glycine-aspartic acid sequences and the disintegrin echistatin. N-Acetyl-D-glucosamine and ß-glucan, which inhibit Mac-1-mediated adhesion to the yeast, blocked lymphocyte adhesion to hyphae. NIH 3T3 fibroblast transfectants expressing human CD11b/CD18 bound to C. albicans, and their binding was inhibited by antibodies specific for CD11b/CD18. Finally, antibodies specific for CD11b/CD18 effectively inhibited the capacity of activated lymphocytes to have an antifungal effect against hyphae. Our results clearly identify Mac-1 (CD11b/CD18) as the lymphocyte surface structure that mediates activated lymphocyte adhesion to C. albicans and the resultant antifungal effect of the lymphocytes.
Present address: Department of Internal Medicine, Section of Rheumatology, Rush-Presbyterian-St. Lukes Medical Center, Chicago, IL 60612.
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