The complement system is made up of numerous small proteins present in the blood, normally synthesized by the liver and usually circulating as inactive precursors. There’re three different signaling pathways to activate the complement system, including the lectin pathway, the classical pathway, and the alternative pathway. The following summarizes several basic functions of the complement system:
-
Opsonization (enhancing phagocytosis of antigens)
-
Chemotaxis (recruiting neutrophils and macrophages)
-
Cell lysis (fracturing membranes of foreign cells)
-
Clumping (antigen-bearing agents)
Complement in Acute Inflammation
Complement components, activated in plasma and humor, are participated in the regulation of virtually all phases of an acute inflammatory response, including the increases in vascular permeability, the changes in vascular caliber and flow, the extravasations of leukocytes, and chemotaxis. A number of regulatory functions of complement have influences on other inflammatory mediators, while other complement activities have connections with the direct behavior of complement proteins on their target cells. Due to its diversity of activating mechanisms, the complement system can independently engage in the control of inflammation, in a way of either the absence or presence of an infection.
Chemotactic Factors
Activation of C3 and C5 is cleaved to release similar bioactive peptides, respectively called anaphylotoxin C3a and C5a. Both are ~10 kDa chemotactic factors, and have vasoactive properties. The C3a and C5a are known for their pro-inflammatory effects. Among them, C5a is a chemotactic factor for neutrophils and is often considered as a mediator of inflammation with robust attractant and activating effects on neutrophils, basophils, and eosinophils, whereas the role of C3a is less described. It has been demonstrated that C3a binds to neutrophil, basophil, and eosinophil leukocytes. This factor induces neutrophil aggregation and morphological changes, with little or no enzyme release.
Complement-mediated Chemotaxis
The main function of complement is protecting the host from infection/inflammation by recruiting (chemotaxis) and enhancing phagocytosis by innate immunity, finally leading to lysis of the target cells. All three pathways cause the production of C3 convertase that cleaves C3 complement into C3a and C3b. C3b cooperates with C3 convertase (C4b2a or C3bBb) to generate C5 convertase, which cleaves C5 protein into C5a and C5b.
The C3a and C5a are critical players in the recruitment of inflammatory cells and secretion of mediators that amplify the inflammation. C5a is likely to be the principal anaphylatoxin mediating inflammation. C5a binds to its receptor C5aR (CD88), which is broadly found on normal cells and inflammatory cells. Except for recruiting the neutrophils, C5a also can increase neutrophil aggregation and adhesiveness. C5a causes the release of pro-inflammatory cytokines and lysosomal enzymes from monocytes and macrophages, thus resulting in chemotaxis.
Leukocytes that cross the wall of blood vessels move toward the sites of injury, guided by chemotactic factors along a chemical gradient. Anaphylatoxins, especially C5a, are well-recognized chemotactic mediators that influence leukocyte migration directly through binding to associated receptors expressed by inflammatory cells. An additional capability of anaphylatoxins is to induce the synthesis of other chemotactic factors, such as chemokines and eicosanoids. C5a stimulates mouse dermal microvascular endothelial cells to form monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-2 (MIP-2). C3a induces the synthesis of MCP-1 and regulated on activation, normal T cells expressed and released in human mast cells. C3a doesn’t function as a chemoattractant for neutrophils, but helps the migration of mast cells and eosinophilic cells. Moreover, C3a and C5a work on their receptors on innate immune cells, taking part in triggering and regulating T cell responses.
Creative Biolabs offers a full range of complement component-related services and products. If you’d like to know more information, please directly contact us and consult our technical supports online.
Related Product
For Research Use Only.
Related Sections:
