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

• Published in: The Journal of immunology (1950) Vol. 162; no. 4; pp. 2281 - 2290
• Main Authors: Xia, Y, Vetvicka, V, Yan, J, Hanikýrová, M, Mayadas, T, Ross, G D
• Format: Journal Article
• Language: English
• Published: United States 15-02-1999
• Subjects: Animals; Binding Sites - immunology; CD18 Antigens - immunology; CD18 Antigens - metabolism; Complement C3b - immunology; Complement C3b - metabolism; Cytotoxicity Tests, Immunologic; Cytotoxicity, Immunologic - immunology; Female; Glucans - immunology; Glucans - metabolism; Killer Cells, Natural - immunology; Kinetics; Lectins - immunology; Lectins - metabolism; Leukemia P388; Lymphocyte Activation - immunology; Macrophage-1 Antigen - genetics; Macrophage-1 Antigen - immunology; Macrophage-1 Antigen - metabolism; Macrophages, Peritoneal - immunology; Macrophages, Peritoneal - metabolism; Mice; Mice, Inbred BALB C; Mice, Inbred Strains; Mice, Knockout; Neutrophils - immunology; Neutrophils - metabolism; Opsonin Proteins - metabolism; Phagocytosis - immunology; Receptors, Immunologic - immunology; Receptors, Immunologic - metabolism; Solubility; Zymosan - immunology; Zymosan - metabolism
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.162.4.2281

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.