Complement C3 but not C5 is required for neutrophil depletion. (A) Inhibition of C5 does not prevent RB6-8C5–induced neutropenia. Blood pressures were measured daily by tail-cuff plethysmography following administration of RB6–8C5 with/without BB5.1 (n ≥ 3, mean ± SEM) by intraperitoneal injection. ***P < .001 versus day 0 using one-way ANOVA and Dunnett posthoc test. (B) C5 inhibition does not prevent neutrophil depletion by RB6-8C5. Neutrophils, monocytes, and lymphocytes were counted on day 3 after injection of RB6-8C5 with or without BB5.1, by differential counting of whole blood. (C) RB6-8C5 and GL113 activate complement in vitro to a comparable extent. Activation of mouse complement by 0.05 mg antibodies was determined by measuring C3 deposition from mouse serum, in antibody-coated wells, using an ELISA (n = 3, mean ± SEM). (D) C3 is required for neutrophil depletion and hypotension. RB6-8C5 was administered to C3^−/− mice for 3 days; then neutrophil levels were determined using differential counting and blood pressure using tail-cuff plethysmography (n = 4-5, mean ± SEM).