|[Frontiers in Bioscience 1, e15-25 March 1, 1996]|
PHARMACOLOGICAL MANIPULATION OF THE COMPLEMENT SYSTEM IN HUMAN
Division of Biochemistry and Immunology, Department of Dermatology, Academisch Medisch Centrum, University of Amsterdam, Amsterdam, The Netherlands
Received 12/08/95; Accepted 26/01/96; On-line 03/01/96
Complement system has recently been reviewed in detail (3-5); only a passing reference of this system will be made here. Activation of complement occurs via classical and alternative pathways. Activation of both pathways serve to covalently opsonize surfaces of foreign invading microorganisms with C3b and/or C4b. C3b and C4b on foreign cell surfaces serve as the building blocks for the formation of C3/C5 convertases of classical and alternative pathways. These convertases amplify the initial deposition of C3b and catalyze the formation of C5b fragment which causes self assembly of C5b-C9 complex, known as membrane attack complex (MAC). This complex causes osmotic lysis of the invading microorganisms. During the activation of both pathways, C3 and C5 breakdown products , C3a and C5a, are formed. These anaphylatoxins play a role in inflammation; they release histamine from mast cells. These products lead to vasodilation and increased vascular permeability. C5a chemotactically attracts neutrophils. C3b and C4b on the surface of the opsonized foreign pathogens act as ligands for complement receptors present on phagocytic cells eventually leading to phagocytosis of the pathogens.