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Complement Metabolism: Cellular and Humoral Regulation

The factors that regulate changes in concentration of plasma proteins are rather complex and as yet poorly understood. It is obvious that at any given time the concentration of a plasma protein is a function of its net rate of biosynthesis, its distribution, and its catabolism. The multiplicity of genetic and non-genetic control mechanisms that affect the balance between synthesis and catabolism complicate analysis of this problem. Nevertheless, during the past fifteen years it has been possible with the use of modem tissue culture and biochemical techniques and the availability of sensitive and specific assays for individual complement proteins to assess in vitro the effect of a nimiber of microenvironmental and genetic parameters on the rates of synthesis of components of the complement system. Methods for the isolation of trace plasma proteins and for labelling of the purified proteins with suitable radionuclides have made it possible to study in vivo the metabolism of several of the complement proteins and to estimate rates of synthesis as well as of catabolism in the presence of several disease states. In our laboratory over the past 10 years we have concentrated on the former method for analysis of regulation of complement metabolism with the recognition that these studies, however detailed, must be translated back to and be consistent with the results of studies of complement metabolism in vivo. Our attention has been focused on several cell types, including gut associated cells (the hepatocyte and epithelial cells of the large and small intestine) and cells of the reticuloendothelial system (those of the monocyte/macrophage series). Studies were initially directed toward defining the site or sites of synthesis of several complement proteins and more recently, the biochemical regulators of complement production. In this re-