Macrophage Complement

Circulating monocytes and tissue macrophages (Me) 1 secrete complement proteins and have distinct receptors for some of these secreted products. Although hepatocytes and possibly epithelial cells are major sources of plasma complement (1), Mcl synthesize C1 subcomponents (2, 3), C4 (4, 5), C2 (5-7) C5 (8), C3 (2, 8) and all the components of the alternative pathway and its control proteins (8). Current evidence indicates that M~ bear at least two distinct receptors for fragments of activated C3 (9, 10). The type one complement receptor, CR1 (205 kD) displays specificity for activated C3 (C3b) (11) and C4 (C4b) (12). CR 1 interacts with iC3b, the product of C3b cleavage by factor I (9), although anti-CR 1 antibodies that block C3b-dependent rosetting do not block iC3b-dependent rosetting (13, 14). The type three complement receptor, CR3, (170 and 95 kD) interacts with iC3b, and possibly with the further degradation product C3dg (9). In order to investigate the physiological role of M¢ complement products we made use of monoclonal antibodies (ab) that are specific for CR1 (13) and that recognize epitopes associated with CR3 (15, 16). We found that deposition of M~-derived C3 on the acceptor surface of zymosan particles mediated binding and ingestion of zymosan via M~ CR3. Zymosan uptake could also be mediated via mannosyl, fucosyl receptors (MFR, 17) in those M~ populations that possess both CR3 and MFR activity (18). These studies indicate a role for M~ complement in local opsonization and host defense.