Cd59

Alexandra Davies and Peter Lachmann, Department of Medicine, University of Cambridge, Medical Research Council Centre, Cambridge, UK

CD59 is an 18 kDa membrane glycoprotein whose primary function is to regulate the activity of the complement membrane attack complex (MAC). Alternative names for CD59 include protectin, membrane inhibitor of reactive lysis (MIRL), homologous restriction factor 20 (HRF20) and membrane attack complex inhibitory factor (MACIF). CD59 is attached to the outer layer of the membrane by a glycosylphosphatidylinositol (GPI) anchor and is very widely distributed (Table 1). It has also been detected in a number of body fluids, but often in association with lipoproteins or small membrane vesicles, and has probably been shed from cell surfaces with its anchor intact or released enzymatically (Table 1). There is no evidence for a secreted form of the protein. The molecule is now extremely well-characterized and species homologs are known in a variety of primates as well as the rat, sheep, pig and mouse. Functionally analogous proteins have also been described in some microorganisms.

CD59 inhibits the formation of the MAC by binding to sites on C8 and C9, thus blocking the uptake and incorporation of multiple C9 molecules into the complex. CD59 from any given species interacts with C8 and C9 from heterologous species with variable efficiency, working best with homologous proteins.

Table 1 Cells and tissues expressing CD59

Liver

Pancreas

Bile canaliculi

Ductal epithelium

Bile duct

Peripheral nervous system

Lung

Schwann cells

Bronchi and bronchioles

Endothelial cells

Kidney

Neurons

Glomerular capillaries

Eye

Glomerular epithelial cells

Lacrimial gland

Distal tubules

Acinar cells

Collecting ducts

Retinal pigment epithelium

Central nervous system

Cornea and conjunctiva

Myelin

Body fluids

Microglia

Serum (low levels)

Neurons

Urine

Oligodendrocytes

Milk

Astrocytes

Seminal plasma

Neoplastic cells

Cerebrospinal fluid

Melanoma

Saliva

Malignant glioma

Other

Colonic adenocarcinoma

Hematopoietic cells

Thyroid carcinomas

Vascular endothelium

Reproductive system

Prostatic epithelium

Unfertilized oocytes

Nasal epithelium

Preimplantation embryos

Chrondocytes

Amniotic epithelium

Salivary duct

Syncytiotrophoblast

Thyroid follicular cells

This forms the basis for the phenomenon of 'homologous restriction' of lysis, a term used to describe the relative inefficiency with which complement lyses homologous cells. The physiological importance of the complement inhibitory role of CD59 is demonstrated in the acquired hemolytic disease paroxysmal nocturnal hemoglobinuria (PNH; see below), in which affected cells are deficient in CD59 and other complement regulatory proteins and are extremely sensitive to lysis. Roles for CD59 in T cell adhesion and activation have also been proposed but not firmly established.

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