title: Paroxysmal nocturnal hemoglobinuria. Enhanced stimulation of platelets by the terminal complement components is related to the lack of C8bp in the membrane.
abstract: Recently, a protein isolated from the membrane of human E, the so-called C8 binding protein (C8bp), has been described. C8bp is characterized as a 65-kDa protein that binds to C8 and inhibits the C5b-9-mediated lysis in a homologous system. In the present study, membranes of peripheral blood cells were tested for the presence of C8bp by SDS-PAGE and immunoblotting. In all cells a protein band reacting with anti-C8bp was seen, the Mr, however, was only about 50 kDa. To further analyze the 50-kDa protein, we isolated the protein by phenol-water extraction and isoelectric focusing from papain-treated platelets. The isolated protein behaved similar to the E-derived C8bp: it inhibited the lysis of model target cells by C5b-9. To examine the function of C8bp in platelets, we tested platelets from patients suffering from paroxysmal nocturnal hemoglobinuria (PNH). These platelets were deficient in C8bp, being in accordance with their higher lytic susceptibility in vitro. In response to sublytic C5b-9 doses, the PNH platelets released considerably more serotonin and thromboxane B2 than normal platelets. By addition of purified C8bp, the thromboxane B2 release was suppressed, indicating that C8bp not only restricts the lytic complement attack, but also regulates the C5b-9-mediated stimulation of target cells. Thus, lack of C8bp might not only result in enhanced hemolysis, but also in enhanced stimulation of platelets, which in turn might contribute to the thrombotic complications seen in some PNH-type III patients.
authors: Institut für Immunologie der Universität Heidelberg, West Germany.
authors: P
authors: P
authors: Blaas
authors: B
authors: B
authors: Berger
authors: S
authors: S
authors: Weber
authors: H H
authors: HH
authors: Peter
authors: G M
authors: GM
authors: Hänsch
mesh_terms: D001792:Blood Platelets / Q000502:physiology*; D001798:Blood Proteins / Q000032:analysis*; D018957:CD59 Antigens; D002352:Carrier Proteins; D002462:Cell Membrane / Q000378:metabolism; D003185:Complement C8 / Q000097:blood*; D015938:Complement Membrane Attack Complex; D003165:Complement System Proteins / Q000378:metabolism*; D004910:Erythrocyte Membrane / Q000378:metabolism; D006457:Hemoglobinuria, Paroxysmal / Q000097:blood*; D006461:Hemolysis; D006801:Humans; D011951:Receptors, Complement / Q000097:blood*; D012701:Serotonin / Q000097:blood; D013929:Thromboxane B2 / Q000097:blood
chemical_list: D001798:Blood Proteins; D018957:CD59 Antigens; D002352:Carrier Proteins; D003185:Complement C8; D015938:Complement Membrane Attack Complex; D011951:Receptors, Complement; C051590:CD59 protein, human; D012701:Serotonin; D013929:Thromboxane B2; D003165:Complement System Proteins