[Frontiers in Bioscience 1, e15-25 March 1, 1996]
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CAVEAT LECTOR



PHARMACOLOGICAL MANIPULATION OF THE COMPLEMENT SYSTEM IN HUMAN DISEASES.

Syed Shafi Asghar, Ph.D.

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

3. REGULATION OF COMPLEMENT ACTIVATION

The complement system has powerful cytolytic activity against which individual's own cells (self cells) should be protected. Several proteins have evolved to control the extent of complement activation in fluid phase and surfaces of self cells (for recent reviews see 6-9). The proteins which inhibit complement activation in fluid phase serve to limit the generation of complement fragments such as C4b and C3b. They also render the generated fragments inactive thereby reducing the extent of cellular damage. These proteins include C1-inhibitor (C1-INH) (10,11), C4-binding protein (C4BP) (12-14), factor H (13-15) and factor I (13,14). Some of the fluid phase proteins such as clusterin (16) and vitronectin (17) inhibit the formation of cytolytic MAC. C4b and C3b which have escaped inactivation by fluid phase inhibitors of complement activation and are already fixed to self cells, are inactivated by cell membrane regulators of complement such as decay accelerating factor (DAF) (7,9,18,19), membrane cofactor protein (MCP) (7,9,20) and complement receptor 1 (CR1) (7,9,21,22). Some of the cell membrane proteins, CD59 (7,23-25) and homologous restriction factor (HRF) (7,26), render MAC non-cytolytic while it is being formed on the self cell. Thus, fluid phase inhibitors in conjunction with membrane embedded inhibitors protect cells from autologous complement. The individual functions of these fluid phase and cell surface complement regulatory proteins are summarized in Table 1.

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