CRYPTOCOCCAL POLYSACCHARIDES INDUCE L-SELECTIN SHEDDING AND TUMOR-NECROSIS-FACTOR RECEPTOR LOSS FROM THE SURFACE OF HUMAN NEUTROPHILS

High titers of cryptococcal polysaccharides in the serum and spinal fl uid and the lack of cellular infiltrates in the infected tissues are h allmarks of disseminated cryptococcosis. Cryptococcal polysaccharides given intravenously to mice inhibit the influx of leukocytes into site s injected with inflammatory mediators. The purpose of this investigat ion was to determine if cryptococcal polysaccharides. i.e., glucuronox ylomannan (GXM), galactoxylomannan, and mannoprotein, affect expressio n of molecules on the surface of neutrophils that are important in ext ravasation. GXM in the absence of serum was shown to induce human neut rophils to shed L-selectin, a molecule needed in the first step of neu trophil movement into tissues. In the presence of serum, GXM caused a further shedding of L-selectin. Shedding of L-selectin was evident by reduced amounts of L-selectin on the neutrophils treated with GXM and by increased levels of soluble L-selectin in the GXM-treated neutrophi l supernatants. GXM also stimulated neutrophils to have reduced expres sion of TNF receptor. In contrast, GXM-treated neutrophils showed incr eased levels of CD15 and CD11b, and unchanged CD16 expression. In the absence of serum, galactoxylomannan and mannoprotein did not affect L- selectin, TNF receptor, CD15, CD11b, or CD16 on neutrophils but did in duce loss of L-selectin in the presence of serum. Our results indicate that cryptococcal polysaccharides, especially GXM, can cause shedding of L-selectin from the surface of neutrophils, and this may prevent n eutrophils from attaching to the endothelial cell surfaces. Blockage o f this early step in cell migration from the vessels into tissues may be responsible in part for reduced cellular infiltration into infected tissues of individuals with disseminated cryptococcosis.