Complement: a critical test of its biological importance

Abstract

The biological activities of the more than 30 proteins that comprise the complement system have been elucidated in parallel lines of investigation that resulted in the purification of the proteins and studies of their function in vitro. Twenty years ago, the first complement cDNA clones were generated. Subsequently the structure and chromosomal localization of the complement genes and the primary sequences of their gene products were revealed. For some, even their higher order structure was solved. This work, coupled with studies of complement gene expression, biosynthesis, post-synthetic processing and secretion, contributed to an analysis of the relatively rare naturally occurring genetic deficiencies of complement proteins discovered fortuitously in humans sand experimental animals. Not until the past 5 years, with the application of methods for manipulating genes in vivo (targeted deletion and overexpression), has it been possible to definitively assign specific functions to complement proteins and to assess their importance in the intact organism. These relatively recent studies have confirmed the in vitro work or revealed unexpected roles for complement effector and regulatory proteins in host defenses, specific immunity, immunopathology, metabolism and reproductive biology This work is reviewed and the implications for understanding human diseases and the design of novel pharmaceutical agents are discussed. The promise of this line of investigation is certain but the context imposed by gender, developmental stage, other genes and environment must be taken into account before the practical implications of this deeper understanding of complement biology are fully realized.

The Role of Complement in Pregnancy and Fetal Loss

“…[3,4] Activation of complement promotes chemotaxis of inflammatory cells and generates proteolytic fragments that enhance phagocytosis by polymorphonuclear leukocytes (PMN) and monocytes. Such lysis of cells and organisms identified as foreign is mediated by the formation of the membrane attack complex (MAC).…”

Recurrent pregnancy loss: the key potential mechanisms

“…The complement system consists of a series of serum proteins that help to regulate the immune response and the inflammatory process by generating fragments that promote chemotaxis, phagocytosis, cell activation and cell lysis [27]. This complex system provides one of the early defense mechanisms against pathogens, and the activation of complement is not detrimental for the host.…”

Antiphospholipid antibodies and pregnancy loss: a disorder of inflammation

“…The complement system, composed of over 30 proteins that act in concert to protect the host against invading organisms, initiates inflammation and tissue injury (Figure 1) (Abbas et al, 2000;Schmidt and Colten, 2000). Complement activation promotes recruitment and activation of inflammatory cells.…”