The beta-glucan-binding lectin site of mouse CR3 (CD11b/CD18) and its function in generating a primed state of the receptor that mediates cytotoxic activation in response to iC3b-opsonized target cells.
Mouse leukocyte CR3 (Mac-1, alphaMbeta2 integrin) was shown to function as a receptor for beta-glucans in the same way as human CR3. Soluble zymosan polysaccharide (SZP) or pure beta-glucans labeled with FITC or 125I bound in a saturable and reversible manner to neutrophils, macrophages, and NK cells. This lectin activity was blocked by anti-CD11b mAb M1/70 or 5C6 and did not occur with leukocytes from CR3-/- (CD11b-deficient) mice. SZP preparations containing primarily mannose or glucose bound to CR3, and the binding of 125I-labeled beta-glucan to CR3 was competitively inhibited by beta-glucans from barley or seaweed, but not by yeast alpha-mannan. Also, as with human CR3, the lectin site of mouse CR3 was inhibited by alpha- or beta-methylglucoside (but not D-glucose), alpha- or beta-methylmannoside, and N-acetyl-D-glucosamine. Phagocytosis of zymosan and serum-opsonized zymosan was partially inhibited by anti-CR3 and was reduced to <40% of normal with leukocytes from CR3-/- mice. As with neutrophils from patients with CD18 deficiency, neutrophils from CR3-/- mice exhibited no phagocytosis of particulate beta-glucan. SZP or beta-glucans primed CR3 of neutrophils, macrophages, and NK cells for cytotoxicity of iC3b-opsonized tumor cells that otherwise did not trigger killing. beta-Glucan priming for cytotoxicity was inhibited by anti-CR3 and did not occur with leukocytes from CR3-/- mice. The primed state of macrophage and NK cell CR3 remained detectable for 18 to 24 h after pulsing with beta-glucans. The similarity of mouse and human CR3 in response to beta-glucans highlights the utility of mouse tumor models for development of therapeutic beta-glucans.
Xia
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Division of Experimental Immunology and Immunopathology, Department of Pathology, University of Louisville, KY 40292, USA. y0xia001@gwise.louisville.edu
Vetvicka
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V
Yan
J
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Hanikýrová
M
M
Mayadas
T
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Ross
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GD
D000818:Animals; D001665:Binding Sites / Q000276:immunology; D018821:CD18 Antigens / Q000276:immunology / Q000378:metabolism*; D003179:Complement C3b / Q000276:immunology* / Q000378:metabolism; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D005260:Female; D005936:Glucans / Q000276:immunology / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000276:immunology; D007700:Kinetics; D037102:Lectins / Q000276:immunology / Q000378:metabolism*; D007941:Leukemia P388; D008213:Lymphocyte Activation / Q000276:immunology*; D016177:Macrophage-1 Antigen / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D009895:Opsonin Proteins / Q000378:metabolism; D010587:Phagocytosis / Q000276:immunology; D011971:Receptors, Immunologic / Q000276:immunology / Q000378:metabolism*; D012995:Solubility; D015054:Zymosan / Q000276:immunology / Q000378:metabolism