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



Bile canaliculi

Ductal epithelium

Bile duct

Peripheral nervous system


Schwann cells

Bronchi and bronchioles

Endothelial cells



Glomerular capillaries


Glomerular epithelial cells

Lacrimial gland

Distal tubules

Acinar cells

Collecting ducts

Retinal pigment epithelium

Central nervous system

Cornea and conjunctiva


Body fluids


Serum (low levels)






Seminal plasma

Neoplastic cells

Cerebrospinal fluid



Malignant glioma


Colonic adenocarcinoma

Hematopoietic cells

Thyroid carcinomas

Vascular endothelium

Reproductive system

Prostatic epithelium

Unfertilized oocytes

Nasal epithelium

Preimplantation embryos


Amniotic epithelium

Salivary duct


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.

Peripheral Neuropathy Natural Treatment Options

Peripheral Neuropathy Natural Treatment Options

This guide will help millions of people understand this condition so that they can take control of their lives and make informed decisions. The ebook covers information on a vast number of different types of neuropathy. In addition, it will be a useful resource for their families, caregivers, and health care providers.

Get My Free Ebook

Post a comment