Intestinal glycoprotein activates the alternative complement pathway by reacting with factor H.
Previous observations indicating complement activation via the alternative pathway of chelated human serum by a rat intestinal glycoprotein fraction were substantiated by using C2-deficient serum. Some inactivation of C6 by the glycoprotein was observed both in normal and C2-deficient serum. As estimated by conglutination, the glycoprotein largely abolished the ability of serum to convert EAC3b to EAC3bi, indicating inhibition of the control factors H (beta 1H globulin) and I (C3bINA), or inhibition of C3b deposition on the cells. The glycoprotein caused no change in the electrophoretic mobility of factors H or I. By immunoelectrophoresis the glycoprotein interfered with the precipitation line of plasminogen and beta-lipoprotein and some other serum proteins. The absence of plasminogen or beta-lipoprotein in serum seemed unimportant for the C3 conversion by the glycoprotein. Factor H was retained when heat-inactivated serum, heat-inactivated serum depleted of 99% albumin or 85% IgG, or heat-inactivated hypogammaglobulinaemic serum was eluted through a column of the intestinal glycoprotein coupled to epoxy-activated Sepharose 6B. Presence of EDTA abolished factor H retention. Factor H from methylamine-treated serum was also adsorbed to the glycoprotein. When serum depleted at 5 degrees C or 31% of the factor H content was heated, the alternative pathway was activated spontaneously. Addition of some of the previously removed factor H reduced the C3 and factor B conversion rate.
D000818:Animals; D002432:Cecum / Q000032:analysis; D002847:Chromatography, Agarose; D003167:Complement Activation / Q000187:drug effects*; D003176:Complement C3 / Q000378:metabolism; D003180:Complement C3b Inactivator Proteins / Q000378:metabolism*; D003183:Complement C6 / Q000378:metabolism; D011415:Complement Factor B / Q000378:metabolism; D017242:Complement Factor H; D003168:Complement Fixation Tests; D003170:Complement Pathway, Alternative / Q000187:drug effects*; D006023:Glycoproteins / Q000494:pharmacology*; D006801:Humans; D007122:Immunoelectrophoresis; D008077:Lipoproteins, LDL / Q000172:deficiency; D010958:Plasminogen / Q000172:deficiency; D051381:Rats; D011919:Rats, Inbred Strains
C493495:CFH protein, human; D003176:Complement C3; D003180:Complement C3b Inactivator Proteins; D003183:Complement C6; D006023:Glycoproteins; D008077:Lipoproteins, LDL; D017242:Complement Factor H; D010958:Plasminogen; D011415:Complement Factor B