CRYPTOCOCCAL POLYSACCHARIDES BIND TO CD18 ON HUMAN NEUTROPHILS

CD18, the beta chain of the beta 2 integrin family of adhesion molecul es, is associated with three different alpha chains (CD11a, -b, and -c ) and is expressed on the surface of all types of leukocytes, CD18-con taining molecules are up-regulated on the surface of neutrophils (poly morphonuclear cells [PMN]) in response to chemotactic agents and are i mplicated 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 inj ected into the bloodstream of mice to simulate the antigenemia in cryp tococcosis, inhibits PR IN accumulation at the site of an inflammatory stimulus, In the present study, we assessed the ability of CneF and i ts individual components, i.e., glucuronoxylomannan (GXM), galactoxylo mannan (GalXM), and mannoprotein (MP), to interact with CD18 on human PMN, CneF labeled with C-14 was shown to bind to human PMN in a dose-d ependent manner, Pretreatment of PMN with anti-CD18, but not an isotyp e-matched control monoclonal antibody (MAb) or anti-CD11a MAb, blocked the binding of C-14-labeled CneF to PMN, In addition, CneF, GXM, and GalXM but not MP significantly blocked the binding of the anti-CD18 MA b to CD18 on the surface of unactivated and formyl methionyl leucyl ph enylalanine-activated PMN as determined by indirect immunofluorescence staining and flow cytometric analysis, In the same experiments, the c ryptococcal polysaccharides did not affect the binding of an anti-CD11 a or anti-L-selectin MAb to the surface of PMN at 4 degrees C. The res ults suggest that CneF and its components GXM and GalXM bind to CD18 o n 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 inf iltration into inflammatory sites.