502 Complement Component and Regulatory Protein Synthesis

Act iva t ion of the classical co mp le me n t p a t h w a y occurs when i m m u n e complexes in teract wi th the first componen t , C 1, to convert it from its inact ive precursor form to an act ive esterolyt ic enzyme, C I . 1 C I by p r o d u c i n g l i m i t e d proteolysis of C4 a n d C2 produces the classical p a t h w a y (23 convertase, C42 (1). T h e a l te rna t ive p a t h w a y is ac t iva ted when the complex surface polysacchar ides of bac te r ia or yeasts come into contac t wi th serum (2). As a consequence of this contact , C3b, the ma jo r c leavage p roduc t of C3; factors B (B) 2 a n d D (17)); and p rope rd in (P) in teract to assemble the a l te rna t ive p a t h w a y C3 a n d C5 convertases (3, 4). Ac t iva t ion of the complemen t system results in the genera t ion o f phlogis t ic molecules from C2, B, C3, a n d (35 which act on the membranes of lymphocytes , macrophages , p o l y m o r p h o n u c l e a r leukocytes, mast cells, platelets , and smooth muscle cells (5), all o f which m a y be involved in the i n f l ammato ry response. M o d u l a t i o n of complemen t ac t iva t ion is achieved by at least three p l a sma proteins: C l i n h i b i t o r which s to ichiometr ica l ly inhibi ts (31 (6), C3b inac t iva tor (C3BINA), which enzymat ica l ly inact ivates C3b (7, 8), a n d f l l H g lobul in which by b ind ing to C3b, displaces B b from the a l te rna t ive p a t h w a y (33 a n d (35 convertases, prevents (33b from in te rac t ing with B and C5, a n d potent ia tes the inac t iva t ion of C3b by C 3 b I N A (9, 10). In h u m a n serum there is usual ly good corre la t ion between concent ra t ions of the