The alternative pathway, the phylogenetically oldest and most important activation pathway of the complement system, provides a highly efficient defence mechanism against invading microorganisms and bacteria. Formation of C3b occurs spontaneously and continuously, while the further activation of this central component is tightly controlled by a large number of both soluble and membrane-bound regulatory proteins. These regulators restrict activation to the surface of foreign cells and microorganisms and simultaneously protect self cells from the destructive effects of this defence system. If left uncontrolled, the activated alternative pathway deposits C3b molecules on the surface of infectious agents (microorganisms) to prepare them for phagocytosis or lysis, and the activation products (chemotactic anaphylatoxins) induce inflammatory reactions by recruiting and stimulating immune effector cells.
Complement Factor D, also known as adipsin, is a highly specific serine protease that cleaves factor B as its only substrate. It is the rate-limiting step of the alternative pathway of complement. The serine protease factor D is a 24-kDa single-chain protein present in human plasma at a rather low concentration. Apparently complement factor D circulates in plasma in an active form. The human protein displays a 60% amino acid homology to mouse adipsin, a mouse serine protease expressed in adipocytes which functions in lipid metabolism.
1. Gavriilaki E, et al. (2015). Small Molecule Factor D Inhibitors Block Complement Activation in Paroxysmal Nocturnal Hemoglobinuria and Atypical Hemolytic Uremic Syndrome. Blood, 126(23), 275-275.
2. Pangburn M K, et al. (1984). The alternative pathway of complement. In Springer seminars in immunopathology (Vol. 7, No. 2-3, pp. 163-192). Springer-Verlag.