Decayaccelerating Factor Cd55

Taroh Kinoshita, Department of Immunoregulation, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan

Copyright © 1998 Elsevier Ltd. All Rights Reserved.

Decay-accelerating factor (DAF), also termed CD55, is a glycoprotein of 65-70 kDa expressed on the surface of all blood cells, vascular endothelial cells and various other tissue cells. It is one of the membrane-bound complement inhibitors that protect host cells from the destructive action of autologous complement. An inherent characteristic of complement is that its active fragments or their complexes can bind to host cell surfaces accidentally or physiologically. This potentially harmful characteristic is prevented by widely distributed membrane-bound complement inhibitors, such as DAF, membrane cofactor protein (MCP or CD46; a 45-70 kDa cofactor for the C3b/C4b-cleaving enzyme factor I) and CD59 (an 18 kDa inhibitor of the membrane attack complex; also termed MACIF, HRF20 or MIRL). A primary function of DAF is to inhibit C3 convertases (C4b2a and C3bBb) and C5 convertases (C4b2a3b and C3bBb3b) on the cell surface; DAF interacts with the convertases and destabilizes them by inducing rapid dissociation of a catalytic subunit C2a or Bb. The inhibitory action of DAF is restricted to C3/C5 convertases bound directly to host cells; that is, DAF does not inhibit normal complement activation on targets, such as microorganisms and immune complexes.

The peptide portion of DAF consists of four tandem repeats of about 60 amino acids, called short consensus repeats (SCRs), followed by a Ser/Thr-rich region of about 70 amino acids. The SCRs are present in 14 complement proteins that bind to C3, C4 or C5 and in other noncomplement proteins. The Ser/Thr-rich region contains multiple O-glycosyl-ation sites. One N-glycosylation occurs in SCRs. A glycolipid anchor covalently linked to the C-terminus of the peptide attaches the protein to the membrane. The glycolipid anchor consists of ethanolamine, which connects the anchor to the peptide, and three mannose residues, glucosamine and phosphatidyl-inositol, which is attached to the membrane. This glycolipid structure, called glycosylphosphatidylino-sitol, is a membrane anchor in 100 or more mem brane proteins, such as alkaline phosphatase, acetylcholinesterase, Thy-1, the variant surface glycoprotein of Trypanosoma brucei and CD59.

In a soluble form, DAF is present in urine, plasma, tears and saliva. Soluble DAF may be released from membrane DAF by the action of phospholipase C or D, or a protease. Soluble DAF has about 100-fold less activity than membrane DAF on cell-bound C3 convertases, and its physiologic function is unknown.

The DAF gene is located in chromosome 1 in band q32 within a cluster of genes of complement regulatory proteins that include SCRs; i.e. factor H, C4-binding protein, MCP, complement receptor 1 (CR1) and 2 (CR2). DAF bears Cromer blood group antigens. Rare individuals called Inab or IFC-lacking Cromer-related antigens are deficient in DAF.

Blood cells of patients with an acquired hemolytic anemia, paroxysmal nocturnal hemoglobinuria (PNH), are deficient in DAF. In the clonal disorder, PNH, abnormal totipotent or pluripotent hematopoietic stem cells give rise to abnormal blood cells showing deficient surface expression of glycosyl-phosphatidylinositol-anchored membrane proteins. Because of this surface deficiency of DAF and CD59, in PNH a fraction of the red cells is susceptible to complement, resulting in intravascular hemolysis and hemoglobinuria.

DAF acts as a receptor for some microorganisms. Echoviruses of various serotypes, including 6, 7, 11, 12, 20 and 21 and coxsackieviruses Bl, B3 and B5, use DAF as a receptor for cell attachment. Uro-pathogenic Escherichia coli binds to cell surface DAF with its fimbriae-like adhesin.

Mouse DAF, which inhibits C3 convertases, has been purified and molecularly cloned. Similarly to human DAF, it consists of four SCRs, a Ser/Thr-rich domain and a glycosylphosphatidylinositol anchor. There is another closely related mouse DAF gene whose product has transmembrane and cytoplasmic domains instead of a glycosylphosphatidylinositol anchor. Two genes are tandemly organized within mouse chromosome 1 near the C4-binding protein gene. Mouse Crry/p65 is a 65 kDa protein bearing both DAF- and MCP-like functions and consisting of five SCRs and transmembrane and cytoplasmic domains. The significance of functional redundancy among these mouse regulatory proteins requires clarification.

See also: CD59; Complement, alternative pathway; Complement, classical pathway; Complement, membrane attack pathway; Thy-1.

How To Bolster Your Immune System

How To Bolster Your Immune System

All Natural Immune Boosters Proven To Fight Infection, Disease And More. Discover A Natural, Safe Effective Way To Boost Your Immune System Using Ingredients From Your Kitchen Cupboard. The only common sense, no holds barred guide to hit the market today no gimmicks, no pills, just old fashioned common sense remedies to cure colds, influenza, viral infections and more.

Get My Free Audio Book

Post a comment