Cryptococcal polysaccharides bind to CD18 on human neutrophils.
CD18, the beta chain of the beta 2 integrin family of adhesion molecules, is associated with three different alpha chains (CD11a, -b, and -c) and is expressed on the surface of all types of leukocytes. CD18-containing molecules are up-regulated on the surface of neutrophils (polymorphonuclear cells [PMN]) in response to chemotactic agents and are implicated in mediating adhesion to an inflamed endothelium, which is a prerequisite to migration of PMN into infected tissues. In a previous study, we found that a cryptococcal culture filtrate (CneF), when injected into the bloodstream of mice to simulate the antigenemia in cryptococcosis, inhibits PMN accumulation at the site of an inflammatory stimulus. In the present study, we assessed the ability of CneF and its individual components, i.e., glucuronoxylomannan (GXM), galactoxylomannan (GalXM), and mannoprotein (MP), to interact with CD18 on human PMN. CneF labeled with 14C was shown to bind to human PMN in a dose-dependent manner. Pretreatment of PMN with anti-CD18, but not an isotype-matched control monoclonal antibody (MAb) or anti-CD11a MAb, blocked the binding of 14C-labeled CneF to PMN. In addition, CneF, GXM, and GalXM but not MP significantly blocked the binding of the anti-CD18 MAb to CD18 on the surface of unactivated and formyl methionyl leucyl phenylalanine-activated PMN as determined by indirect immunofluorescence staining and flow cytometric analysis. In the same experiments, the cryptococcal polysaccharides did not affect the binding of an anti-CD11a or anti-L-selectin MAb to the surface of PMN at 4 degrees C. The results suggest that CneF and its components GXM and GalXM bind to CD18 on human PMN. Based on our findings, we propose that CD18 is a possible molecular target of cryptococcal polysaccharides and that binding of the polysaccharides to CD18 has the potential to inhibit leukocyte infiltration into inflammatory sites.
Dong
Z M
ZM
Department of Microbiology and Immunology, University of Oklahoma Health Science Center, Oklahoma City 73190, USA.
Murphy
J W
JW
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001666:Binding Sites, Antibody / Q000187:drug effects; D001667:Binding, Competitive; D018821:CD18 Antigens / Q000096:biosynthesis / Q000097:blood / Q000378:metabolism*; D002474:Cell-Free System / Q000276:immunology / Q000378:metabolism; D003455:Cryptococcus neoformans / Q000254:growth & development / Q000378:metabolism*; D003470:Culture Media / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D019041:L-Selectin / Q000096:biosynthesis / Q000187:drug effects; D016169:Lymphocyte Function-Associated Antigen-1 / Q000096:biosynthesis / Q000187:drug effects; D016177:Macrophage-1 Antigen / Q000096:biosynthesis / Q000187:drug effects; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D018375:Neutrophil Activation / Q000276:immunology; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism*; D011134:Polysaccharides / Q000276:immunology* / Q000378:metabolism* / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D018821:CD18 Antigens; D003470:Culture Media; D016169:Lymphocyte Function-Associated Antigen-1; D016177:Macrophage-1 Antigen; D011134:Polysaccharides; D019041:L-Selectin; D009240:N-Formylmethionine Leucyl-Phenylalanine; C027478:glucuronoxylomannan