COMPLEMENT BIOSYNTHESIS IN THE CENTRAL-NERVOUS-SYSTEM

Complement is an important effector arm of the human immune response. Binding of proteolytic fragments derived from activation of complement by specific receptors leads to responses as diverse as inflammation, opsonization, and B-cell activation. The importance of characterizing the expression and regulation of complement in the CNS is highlighted by growing evidence that complement plays a significant role in the pa thogenesis of a variety of neurological diseases, such as multiple scl erosis and Alzheimer's disease. In vitro studies have demonstrated tha t astrocytes, the predominant glial cell type in the brain, are capabl e of expressing or producing a majority of the components of the compl ement system. Expression of many complement proteins synthesized by as trocytes is regulated by both pro- and anti-inflammatory cytokines, ma ny of which are also produced by several cell types in the CNS. In add ition to astrocytes, ependymal cells, endothelial cells, microglia, an d neurons have recently been shown to synthesize various complement pr oteins or express complement receptors on their cell surfaces. Togethe r, these studies demonstrate that several cell types throughout the br ain have the potential to express complement and, in many cases, incre ase expression in response to mediators of the acute phase response. T hese studies suggest that complement may play a greater role in CNS im mune responses than previously thought, and pave the way for better un derstanding of the dynamics of complement expression and regulation in vivo. Such understanding may lead to therapeutic manipulation of comp lement host defense functions in a variety of inflammatory and degener ative diseases in the CNS.