title: Mechanisms for induction of L-selectin loss from T lymphocytes by a cryptococcal polysaccharide, glucuronoxylomannan.
abstract: Disseminated cryptococcosis is accompanied by cryptococcal polysaccharides in the serum and the lack of cellular infiltrates in infected tissues. Cryptococcal polysaccharides given intravenously to mice inhibit the influx of T lymphocytes into the sites of cell-mediated immune response. The focus here was to determine whether cryptococcal polysaccharides modulate the expression of molecules, such as L-selectin, that are important in extravasation of T cells. Cryptococcal glucuronoxylomannan (GXM), but not galactoxylomannan or mannoprotein, was found to cause loss of L-selectin from freshly isolated human T cells of both CD4 and CD8 subsets and from Jurkat cells. With the signaling-pathway inhibitors staurosporine (which inhibits protein kinase C) and herbimycin A (which inhibits protein tyrosine kinases), we showed that GXM or the cryptococcal culture filtrate antigen CneF directly induces L-selectin loss from CD4(+) and CD8(+) T cells via a herbimycin A-sensitive pathway(s) presumably involving one or more protein tyrosine kinases but not via a pathway involving protein kinase C. Loss of L-selectin from the T cells before the T cells have a chance to bind to L-selectin ligands on endothelial cells would be expected to prevent T-cell migration into inflamed tissues and/or lymph organs.
authors.affiliation: Department of Microbiology and Immunology, University of Oklahoma Health Science Center, Oklahoma City 73190, USA.
authors.forename: Z M
authors.initials: ZM
authors.lastname: Dong
authors.forename: L
authors.initials: L
authors.lastname: Jackson
authors.forename: J W
authors.initials: JW
authors.lastname: Murphy
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000946:Antigens, Fungal / Q000502:physiology; D016227:Benzoquinones; D018845:CD11 Antigens / Q000276:immunology; D018821:CD18 Antigens / Q000096:biosynthesis / Q000276:immunology; D018801:CD2 Antigens / Q000096:biosynthesis; D018106:CD28 Antigens / Q000096:biosynthesis / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D015704:CD4 Antigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D003455:Cryptococcus neoformans / Q000254:growth & development / Q000276:immunology*; D003470:Culture Media; D006801:Humans; D019169:Jurkat Cells; D019041:L-Selectin / Q000097:blood / Q000378:metabolism*; D047029:Lactams, Macrocyclic; D017493:Leukocyte Common Antigens / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000276:immunology; D008562:Membrane Glycoproteins / Q000276:immunology / Q000502:physiology; D011134:Polysaccharides / Q000037:antagonists & inhibitors / Q000276:immunology / Q000502:physiology*; D011135:Polysaccharides, Bacterial / Q000276:immunology / Q000502:physiology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011809:Quinones / Q000494:pharmacology; D017828:Rifabutin / Q000031:analogs & derivatives; D019311:Staurosporine / Q000494:pharmacology; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D000946:Antigens, Fungal; D016227:Benzoquinones; D018845:CD11 Antigens; D018821:CD18 Antigens; D018801:CD2 Antigens; D018106:CD28 Antigens; D017252:CD3 Complex; D015704:CD4 Antigens; D003470:Culture Media; D047029:Lactams, Macrocyclic; D008562:Membrane Glycoproteins; D011134:Polysaccharides; D011135:Polysaccharides, Bacterial; D011809:Quinones; C025363:mannoproteins; D019041:L-Selectin; D017828:Rifabutin; C020754:herbimycin; C043689:galactoxylomannan; C027478:glucuronoxylomannan; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C; D017493:Leukocyte Common Antigens; D019311:Staurosporine