Release of C8 binding protein (C8bp) from the cell membrane by phosphatidylinositol-specific phospholipase C.
Erythrocytes from patients with paroxysmal nocturnal hemoglobinuria (PNH) are abnormally sensitive to complement. Two membrane proteins, the C8 binding protein (C8bp) and the decay accelerating factor (DAF), which are expressed on normal cells, function to restrict lysis by homologous complement, and both of these proteins are absent from PNH erythrocytes. DAF is anchored to the plasma membrane on normal cells by a phosphatidylinositol linkage. The investigators found that a purified phosphatidylinositol-specific phospholipase C cleaved C8bp from the surface of normal lymphocytes and monocytes. This finding indicates that the abnormal complement sensitivity of PNH erythrocytes arises from a common defect, the inability to attach the phosphatidylinositol-containing anchor that is necessary for the membrane expression of both membrane complement regulatory proteins, the C8bp, and DAF.
Hänsch
G M
GM
Institut fur Immunologie, Universitat Heidelberg, FRG.
Weller
P F
PF
Nicholson-Weller
A
A
D001426:Bacterial Proteins / Q000502:physiology; D001798:Blood Proteins / Q000032:analysis* / Q000302:isolation & purification; D018957:CD59 Antigens; D002352:Carrier Proteins; D003185:Complement C8 / Q000378:metabolism*; D006801:Humans; D008214:Lymphocytes / Q000032:analysis; D008565:Membrane Proteins / Q000097:blood* / Q000302:isolation & purification; D008970:Molecular Weight; D009000:Monocytes / Q000032:analysis; D010716:Phosphatidylinositols; D013211:Staphylococcus aureus; D010738:Type C Phospholipases / Q000502:physiology*
D001426:Bacterial Proteins; D001798:Blood Proteins; D018957:CD59 Antigens; D002352:Carrier Proteins; D003185:Complement C8; D008565:Membrane Proteins; D010716:Phosphatidylinositols; C051590:CD59 protein, human; D010738:Type C Phospholipases