Complement Regulator of Complement System: Protectin / CD59

Complement Regulator of Complement System: Protectin / CD59 Background

The human CD59 antigen is an 18–25-kDa (in sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE))glycoprotein that inhibits complement lysis. Because of its independent isolation in different laboratories CD59 has been given various names: p18, membrane attack complex inhibiting factor (MACIF), homologous restriction factor 20 (HRF20) membrane inhibitor of reactive lysis (MIRL) and protectin/CD59. CD59 is very widely expressed in human cells and tissues. It is present on all circulating blood cells, endothelial cells, in most epithelial cells and spermatozoa. In normal human heart CD59 is expressed on myocytes but appears to become lost from infarcted myocardium. The expression of CD59 is strong on most types of malignant cells.

Like DAF, CD59 has a GPI anchor. Enzymatic cleavage of the polypeptide from the anchor phospholipid by phospholipase C (PIPLC) or direct release from cell membranes generate soluble forms of CD59. The phospholipid-containing and free forms can be found in human urine, saliva, tears, breast milk, blood plasma, amniotic fluid and seminal plasma in various ratios. In SDS-PAGE gels CD59 appears as a smear of 18-25 kDa. The gene for CD59 is located on chromosome 11p13 and has four exons. The 77 amino acids of protectin constitute together a distinct domain with five internal disulfide bridges.

Protectin inhibits the final steps of membrane attack complex/MAC assembly on cell membranes. By binding to the C5b-8 complex, protectin limits C9 input and prevents formation of the polymeric C9 complex. The binding sites of erythrocyte protectin on C8 and C9 have been localized to the C8 α chain and the C9b fragment. Like DAF, CD59 can readily incorporate into cell membranes. Binding of CD59 has been shown to occur to HIV, Schistosoma mansoni and E. coli outer cell membranes.

Complement Regulator of Complement System: Protectin / CD59 Reference

1. Meri S, et al. (1990). Human protectin (CD59), an 18,000-20,000 MW complement lysis restricting factor, inhibits C5b-8 catalysed insertion of C9 into lipid bilayers. Immunology, 71(1), 1.
2. Meri S, et al. (1991). Distribution of protectin (CD59), a complement membrane attack inhibitor, in normal human tissues. Laboratory investigation; a journal of technical methods and pathology, 65(5), 532-537.
3. Väkevä A, et al. (1992). Loss of expression of protectin (CD59) is associated with complement membrane attack complex deposition in myocardial infarction. Laboratory investigation; a journal of technical methods and pathology, 67(5), 608-616.
4. Konttinen Y T, et al. (1996). Complement in acute and chronic arthritides: assessment of C3c, C9, and protectin (CD59) in synovial membrane. Annals of the rheumatic diseases, 55(12), 888-894.
5. Jarvis G A, et al. (1997). Expression and function of the complement membrane attack complex inhibitor protectin (CD59) in human prostate cancer. International journal of cancer, 71(6), 1049-1055.