Inhibition of complement alternative pathway in mice with Fab antibody to recombinant adipsin/factor D.
Mouse adipsin is a serine protease secreted mainly by adipocytes. Similarly to factor D of human complement, it cleaves factor B. That adipsin is the equivalent of human factor D in the mouse is further suggested by their structural homology. Specific antisera against recombinant mouse adipsin (r-adipsin) were produced in rabbits. Anti-r-adipsin IgG was shown to bind to radiolabeled r-adipsin and to inhibit its hemolytic activity. In vitro, these antibodies Ab and Fab fragments thereof inhibited the adipsin/factor D hemolytic activity of mouse serum. They also blocked C3 activation induced by cobra venom factor (CVF), but did not interfere with classical pathway function. After intravenous injection of anti-r-adipsin Fab into BALB/c mice, the adipsin/factor D hemolytic activity of serum was abolished during a 4-h period. The C3 depleting effect of CVF injected intravenously was significantly delayed in BALB/c mice which had been pretreated with anti-r-adipsin Fab. These experiments demonstrate that mouse adipsin is the only form of mouse factor D and that anti-r-adipsin antibody can be used to produce a specific inhibition of the alternative pathway in vivo.
Laboratory of Immunonephrology (5-222), Centre Médical Universitaire, Geneva, Switzerland.
M
M
Pascual
E
E
Catana
T
T
White
B M
BM
Spiegelman
J A
JA
Schifferli
D000818:Animals; D003176:Complement C3 / Q000378:metabolism; D011416:Complement Factor D / Q000037:antagonists & inhibitors / Q000378:metabolism*; D003170:Complement Pathway, Alternative; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D066298:In Vitro Techniques; D051379:Mice; D008807:Mice, Inbred BALB C; D011994:Recombinant Proteins; D012697:Serine Endopeptidases / Q000276:immunology*
D003176:Complement C3; D007140:Immunoglobulin Fab Fragments; D011994:Recombinant Proteins; D012697:Serine Endopeptidases; C493488:CFD protein, human; D011416:Complement Factor D; C493491:complement factor D, mouse