Complement Regulators: Decay-accelerating Factor

Complement Regulator of Complement System: Decay-accelerating Factor Background

Decay-accelerating factor (CD55 or DAF), is a 70-kDa glycoprotein that is present on the membranes of peripheral blood cells, vascular endothelial cells, placenta and many types of epithelial cells. The extracellular N-terminal part of DAF contains four SCRs and an STP-region. Anchoring of DAF to phospholipids on the cell membrane occurs through a glycosylphosphatidylinositol (GPI) moiety. Soluble forms of decay-accelerating factor/DAF without the anchor phospholipid have been found in many body fluids including plasma, tears, saliva, urine, synovial and cerebrospinal fluids. If decay-accelerating factor/DAF is detached from the cell membranes with an intact GPI-phospholipid tail it can readily reincorporate into new cell membranes. Some release of DAF may occur in vivo.

Decay-accelerating factor (CD55 or DAF), binds to and dissociates both the classical (C4b2a) and the alternative (C3bBb) pathway C3/C5 convertase enzymes. Since DAF has a higher affinity for C4b and C3b when they are in complex with their respective catalytic subunits it can recycle from C4b and C3b sites to active C3 convertase enzymes. In contrast with CR1, DAF acts intrinsically, i.e. it decays C3 convertases on the same cell where it is located.

Compared with MCP and CD59 the expression level of DAF is relatively low but it can be upregulated by various stimuli. On epithelial cells of the urinary tract, decay-accelerating factor/DAF acts as a ligand for the Dr adhesin of certain E. coli strains that cause urinary tract infections. In addition, DAF has been shown to act as a receptor for certain types of echo- and coxsackie B-viruses. Some pathogens, like human immunodeficiency virus (HIV) and Schistosoma mansoni worms, have been found to 'hijack' GPI anchored DAF into their cell membranes in a functionally active form.

Recent studies have shown that the expression level of DAF is increased in many types of malignant tumours. In general, the expression of DAF prevents opsonization, release of complement anaphylatoxins and complement lysis, thereby suppressing inflammatory reactions and tissue destruction. The fact that the complement system acts as the main immune effector mechanism in the hyperacute rejection of xenogeneic organ transplants has resulted in the development of pigs that are transgenic for human DAF. Organs (mainly heart and liver) from these animals have been shown to have a prolonged survival in primate hosts.

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