Production of complement components by cells of the immune system

Abstract

SummaryThe complement system is an important part of the innate immune defence. It contributes not only to local inflammation, removal and killing of pathogens, but it also assists in shaping of the adaptive immune response. Besides a role in inflammation, complement is also involved in physiological processes such as waste disposal and developmental programmes. The complement system comprises several soluble and membrane-bound proteins. The bulk of the soluble proteins is produced mainly by the liver. While several complement proteins are produced by a wide variety of cell types, other complement proteins are produced by only a few related cell types. As these data suggest that local production by specific cell types may have specific functions, more detailed studies have been employed recently analysing the local and even intracellular role of these complement proteins.Here we review the current knowledge about extrahepatic production and/ or secretion of complement components. More specifically, we address what is known about complement synthesis by cells of the human immune system.

Complement in cancer: untangling an intricate relationship

“…The local production of complement proteins by various tissues is well recognized 55,56 (BOX 2). Furthermore, both tumour and stromal cells produce complement proteins, and evidence for local and systemic activation of complement is often observed in cancer settings 57,58 .…”

Characterizing a pH‐switch anti‐C5 antibody as a tool for human and mouse complement C5 purification and cross‐species inhibition of classical and reactive lysis

“…The complement system, a network of over 30 fluid‐phase and cell‐membrane‐bound proteins and regulators, is a critical component of the innate immune defence against infection . Recent studies have broadened our view of complement – a mediator of pleiotropic effects including inflammation, modulation of adaptive immunity, metabolism and neuronal development . Complement activation pathways all lead to the formation of a C3‐cleaving enzyme (C3 convertase; C4b2a or C3bBb) that yields C3a and C3b; addition of C3b to the C3 convertase generates a C5 convertase (C4b2a3b; C3bBbC3b) that cleaves C5, releasing the pro‐inflammatory fragment C5a and initiating membrane attack complex (MAC) formation.…”

Infant onset severe complement‐mediated hemolytic uremic syndrome complicated by secondary sclerosing cholangitis

“…LT is not routinely recommended in CFB mutations. Nevertheless, the alternative complement system components affect each other with a rather complex relationship . Additionally, specific therapies such as TPE and two doses of eculizumab, we think that LT performed in our patient may regulate dysregulated the alternative complement system.…”