Synthesis of complement by macrophages and modulation of their functions through complement activation.
During the last decade considerable progress has been made to characterize intimate functional links between macrophages, a major cellular component of immunoinflammatory responses, and the complement system representing the major humoral mediator of inflammation. Macrophages of various species and tissue sites have been shown to synthesize and release most of the complement components providing these cells with their own "pericellular" complement system. Circumstantial evidence for the assembly of both classical and alternative pathway convertases has been adduced. An intricate network of feedback loops involving endogenous and extrinsic factors operates to adjust complement production to acute requirements, for example augmenting production in the face of accelerated turnover at sites of inflammation, and returning it to baseline levels once the inflammatory stimulus has subsided, in order to maintain a fine-tuned balance. The molecular mechanisms underlying regulation of complement synthesis by macrophages are beginning to be elucidated by use of gene technology. On the other hand, complement activation products exert a number of effects on macrophages via specific surface receptors causing internalization of offending agents, microbes, and immune complexes, promotion of intracellular killing, controlling migration behavior, inducing release of potent biologic substances such as lysosomal enzymes, arachidonic acid metabolites, and interleukin 1. In these interactions, two important humoral mediator systems of inflammation, the complement system and the arachidonic acid cascade, are functionally linked at the level of the macrophage. Stimulation of the release of immunomodulating compounds from macrophages invoke a role for complement in immune regulation. This multifaceted interplay is of particular importance considering the mobility of macrophages that allows them to gain almost unrestricted access to sites of ongoing immunoinflammatory responses. The time seems to have come to abandon the petrified thinking in socalled systems as, for instance, humoral versus cellular, specific versus unspecific, and to proceed to interlocking functions guided by physiology proper.
D000706:Anaphylatoxins / Q000494:pharmacology; D000818:Animals; D003167:Complement Activation; D003172:Complement C1 / Q000096:biosynthesis; D003175:Complement C2 / Q000096:biosynthesis; D003176:Complement C3 / Q000096:biosynthesis / Q000494:pharmacology; D015926:Complement C3a; D003181:Complement C4 / Q000096:biosynthesis; D003182:Complement C5 / Q000096:biosynthesis; D003170:Complement Pathway, Alternative; D003165:Complement System Proteins / Q000096:biosynthesis*; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D008264:Macrophages / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D009000:Monocytes / Q000378:metabolism; D010587:Phagocytosis; D011453:Prostaglandins / Q000378:metabolism; D011951:Receptors, Complement
D000706:Anaphylatoxins; D003172:Complement C1; D003175:Complement C2; D003176:Complement C3; D003181:Complement C4; D003182:Complement C5; D011453:Prostaglandins; D011951:Receptors, Complement; D015926:Complement C3a; D003165:Complement System Proteins