76 Decay - Accelerating Factor in Normal and Pnh

Decay-accelerat ing factor (DAF), 1 which is an inhibi tor o f c o m p l e m e n t and is present on e ry th rocy te membranes , was first descr ibed by H o f f m a n n (1, 2) and later isolated and character ized as an Mr 70,000 prote in by Nicholson-Weller et al. (3). DAF very effectively prevents the amplif ication steps o f the cascade by in ter fer ing with assembly o f the C3-convertases, C4b2a and C3bBb, and the C5convertases, C4b2a3b and C 3bBb3b (3-5). T h e precise mechanism o f action o f DAF is unknown but several lines o f evidence indicate that it binds to C4b or C3b and compet i t ively prevents the interact ion with C2 and factor B. Erythrocyte DAF funct ions only in the m e m b r a n e in which it is located, that is, DAF does not act on C3or C5-convertases f o r m e d on ne ighbor ing cells or on foreign substrates, such as bacter ia and i m m u n e complexes (5). For this reason it has been suggested that the physiological role o f DAF is to pro tec t cells f rom damage by auto logous complement . Th is hypothesis is in a g r e e m e n t with the f inding that e ry throcytes f rom patients with paroxysmal nocturnal hemoglob inur ia (PNH), an acquired syndrome character ized by an unusual susceptibility o f red cells to c o m p l e m e n t activation (6), a re DAF deficient (4, 7-9) . Platelet and leukocyte abnormal i t ies are also found in P N H , but the role o f DAF in these disorders is unclear (10-13) . T h e idea that DAF 's role is to p reven t damage to autologous cells by complement , receives fu r the r suppor t f rom the findings r epo r t ed here. In the present study we used monocional antibodies to measure the amounts of DAF on