Circulating proteins of three interrelated systems—the complement, kinin, and coagulation systems—are involved in several aspects of the inflammatory reaction.Complement The complement system consists of plasma proteins that play an important role in host defense (immunity) and inflammation. Upon activation, different complement proteins coat (opsonize) particles, such as microbes, for phagocytosis and destruction, and contribute to the inflammatory response by increasing vascular permeability and leukocyte chemotaxis. Complement activation ultimately generates a porelike membrane attack complex (MAC) that punches holes in the membranes of invading microbes. Here we summarize the role of the complement system in inflammation. • Complement components, numbered C1 to C9, are present in plasma in inactive forms, and many of them are activated by proteolysis to acquire their own proteolytic activity, thus setting up an enzymatic cascade. • The critical step in the generation of biologically active complement products is the activation of the third component, C3 (Fig. 2–18). C3 cleavage occurs by three pathways: (1) the classical pathway, triggered by fixation of the first complement component C1 to antigen-antibody complexes; (2) the alternative pathway, triggered by bacterial polysaccharides (e.g., endotoxin) and other microbial cell wall components, and involving a distinct set of plasma proteins including properdin and factors B and D; and (3) the lectin pathway, in which a plasma lectin binds to mannose residues on microbes and activates an early component of the classical pathway (but in the absence of antibodies). • All three pathways lead to the formation of a C3 convertase that cleaves C3 to C3a and C3b. C3b deposits on the cell or microbial surface where complement was activated and then binds to the C3 convertase complex to form C5 convertase; this complex cleaves C5 to generate C5a and C5b and initiate the final stages of assembly of C6 to C9.
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