The b-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, aMb2 integrin) was shown to function as a receptor for b-glucans in the same way as human CR3. Soluble zymosan polysaccharide (SZP) or pure b-glucans labeled with FITC or I 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 I-labeled b-glucan to CR3 was competitively inhibited by b-glucans from barley or seaweed, but not by yeast a-mannan. Also, as with human CR3, the lectin site of mouse CR3 was inhibited by aor b-methylglucoside (but not D-glucose), aor b-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 b-glucan. SZP or b-glucans primed CR3 of neutrophils, macrophages, and NK cells for cytotoxicity of iC3b-opsonized tumor cells that otherwise did not trigger killing. b-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 b-glucans. The similarity of mouse and human CR3 in response to b-glucans highlights the utility of mouse tumor models for development of therapeutic b-glucans. The Journal of Immunology, 1999, 162: 2281–2290.