Inflammatory Products of the Complement Pathway

The complement system, originally described as a defense system limited to pathogen removal, is now identified as a main contributor to many basic immunological processes and is critically involved in the inflammatory response. Activation of the complement system is triggered by the presence of pathogen, altered or injured cells or other irritants and leads to the proteolytic activation of complement components C3 and C5 and generation of biologically active anaphylatoxins (C3a and C5a) and opsonins (C3b and C4b). Receptors for these molecules are expressed on a wide range of immune cells, and the engagement of complement activation fragment receptors on these cells mediates the acute inflammatory response that leads to clearance of the pathogen/irritant. Importantly, controlled complement activation also contributes to the resolution phase of inflammation and tissue repair. However, complement also modulates the functions of B and T cells, and when complement activation is dysregulated, it can thus contribute to chronic inflammation, which is mostly driven by adaptive immunity. This article gives an overview of the acknowledged contributions of the complement system to inflammation and also introduces briefly current paradigm shifts in the field that point to an even more expansive role for complement in inflammatory responses.