Mechanisms for induction of L-selectin loss from T lymphocytes by a cryptococcal polysaccharide, glucuronoxylomannan.
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.
Dong
Z M
ZM
Department of Microbiology and Immunology, University of Oklahoma Health Science Center, Oklahoma City 73190, USA.
Jackson
L
L
Murphy
J W
JW
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*
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