Complement and Inflammation

Inflammation is a programmed response to tissue injury and microbial agents. In primitive multicellular organisms, humoral and cellular constituents of host defenses are focused by the presence of a foreign body or at a site of tissue injury. The evolution in higher organisms of a discrete circulatory system introduced complexity that imposed a need for mechanisms regulating changes in permeability of the circulatory system and for margination/directed migration of circulating cellular elements. For instance, an array of regulated genes expressed in endothelium, blood leukocytes, and in extra- vascular cells direct the accumulation of white cells to sites of inflammation. Proteins within the selectin family (McEver 1991) displayed on the majority of lymphocytes, neutrophils, monocytes, and the corresponding cytokine- regulated proteins on endothelium, are critical for the recruitment of white cells to an inflammatory site. Similar general functions are served by adhesion molecules of the integrin and immunoglobulin (Ig) families (Springer 1990; Kishimoto et al. 1989).Small molecular species such as nitric oxide (Kubes et al. 1991), arachadonic acid metabolites (Smith et al. 1980), and reactive oxygen radicals (Patel 1991) generated at inflammatory sites, play modulating and direct roles in leukocyte adherence, migration, activation. This process involves elaborate control mechanisms and is highly redundant even when considering only the intravascular elements. In addition, separate vascular and peripheral tissue sources of the critical constituents evolved. This has resulted in separate regulatory mechanisms that govern availability of the intravascular and extravascular components of the inflammatory response.