Complement: Functions, location and implications

Abstract

The complement system, an arm of the innate immune system plays a critical role in both health and disease. The complement system is highly complex with dual possibilities, helping or hurting the host, depending on the location and local microenvironment. The traditionally known functions of complement include surveillance, pathogen recognition, immune complex trafficking, processing and pathogen elimination. The noncanonical functions of the complement system include their roles in development, differentiation, local homeostasis and other cellular functions. Complement proteins are present in both, the plasma and on the membranes. Complement activation occurs both extra‐ and intracellularly, which leads to considerable pleiotropy in their activity. In order to design more desirable and effective therapies, it is important to understand the different functions of complement, and its location‐based and tissue‐specific responses. This manuscript will provide a brief overview into the complex nature of the complement cascade, outlining some of their complement‐independent functions, their effects at different locale, and their implication in disease settings.

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“…The complement system comprises a network of over 30 proteins, which interact in a sequential and regulated manner, culminating in the formation of the membrane attack complex (MAC). The MAC inserts into cell membranes, leading to pore formation and cell damage ( 286 ). The classical complement pathway is activated by antibody-antigen complexes (see chapter 3).…”

The Production of Complement Inhibitor Proteins in Mammalian Cell Lines—Light at the End of the Tunnel?

“…The activity of the complement system has traditionally been attributed to its presence in the circulatory system, but on the basis of accumulated knowledge [43][44][45], separate intracellular [46][47][48], lung [23] and gut (mucosal) [34], neuronal [49,50], tumor microenvironment [51] and breast milk [35,52,53] complement systems can be defined, characterized by the local production of (sometimes non-canonical) components and unique functions (Figure 2). This explosion of knowledge has led to the identification of new drug targets and inhibitor candidates, boosting research funding and also driving investment by Big Pharma.…”