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Complement-mediated tissue injury in humans occurs upon deposition of immune complexes, such as in autoimmune diseases and acute respiratory distress syndrome. Acute lung inflammatory injury in wild-type and C3^−/− mice after deposition of IgG immune complexes was of equivalent intensity and was C5a dependent, but injury was greatly attenuated in Hc^−/− mice (Hc encodes C5). Injury in lungs of C3^−/− mice and C5a levels in bronchoalveolar lavage (BAL) fluids from these mice were greatly reduced in the presence of antithrombin III (ATIII) or hirudin but were not reduced in similarly treated C3^+/+ mice. Plasma from C3^−/− mice contained threefold higher levels of thrombin activity compared to plasma from C3^+/+ mice. There were higher levels of F2 mRNA (encoding prothrombin) as well as prothrombin and thrombin protein in liver of C3^−/− mice compared to C3^+/+ mice. A potent solid-phase C5 …