title: Local inflammation caused by a monoclonal antibody that blocks the function of the rat membrane inhibitor of C3 convertase.
abstract: The participation of membrane inhibitors in C-mediated inflammation in vivo was analyzed in rats with the use of mAbs against membrane inhibitors of C. 512Ag inhibits C3 convertase of homologous rat C and rat CD59 prevents the formation of homologous membrane attack complexes. The histologic distributions of 512Ag and CD59 in rat skin were essentially the same. However, although intracutaneous administration of mAb against 512Ag (anti-512Ag) in the form of F(ab')2 induced a remarkable inflammatory response visualized by exudation of Evans blue that had been previously injected i.v., the mAb against CD59 caused no inflammatory exudate. Furthermore, anti-512Ag F(ab')2 caused deposition of C3 followed by intense polymorphonuclear leukocyte infiltration and hemorrhage at the injection sites within 24 h. This reaction was completely abrogated by depletion of C. Therefore, spontaneous C activation on self cell membranes requires amplification at the C3 convertase step, which is restricted by membrane inhibitors such as 512Ag, thus preventing inflammation. A type II allergic response might preferentially occur at sites that exhibit an impairment of membrane inhibitor(s) of C3 convertase. However, although depletion of leukocytes by preadministration of cyclophosphamide did not reduce C3 deposition by anti-512Ag. Evans blue exudation was appreciably reduced, indicating that infiltrated leukocytes play a role in enhancing and prolonging inflammation initiated by local C activation.
authors.affiliation: Third Department of Internal Medicine, Nagoya University School of Medicine, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Nishikawa
authors.forename: S
authors.initials: S
authors.lastname: Matsuo
authors.forename: N
authors.initials: N
authors.lastname: Okada
authors.forename: B P
authors.initials: BP
authors.lastname: Morgan
authors.forename: H
authors.initials: H
authors.lastname: Okada
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D000954:Antigens, Surface; D001667:Binding, Competitive; D018957:CD59 Antigens / Q000032:analysis; D003167:Complement Activation; D050577:Complement C3-C5 Convertases / Q000037:antagonists & inhibitors* / Q000276:immunology*; D003169:Complement Inactivator Proteins / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000502:physiology; D003165:Complement System Proteins / Q000172:deficiency; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000032:analysis; D006967:Hypersensitivity / Q000097:blood / Q000473:pathology; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D007970:Leukopenia / Q000276:immunology / Q000473:pathology; D008565:Membrane Proteins / Q000097:blood / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011956:Receptors, Cell Surface; D011951:Receptors, Complement / Q000032:analysis; D012867:Skin / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D018957:CD59 Antigens; D003169:Complement Inactivator Proteins; C513105:Cr1l protein, rat; D015395:Histocompatibility Antigens Class I; D007140:Immunoglobulin Fab Fragments; D008565:Membrane Proteins; D011956:Receptors, Cell Surface; D011951:Receptors, Complement; D003165:Complement System Proteins; D050577:Complement C3-C5 Convertases