Local tissue injury induced by glucose oxidase conjugated with anti-collagen antibody.
The conjugation of glucose oxidase with anti-collagen antibody using periodate oxidation of the enzyme carbohydrate moiety is described. After conjugation, the antibody retained its antigen-binding capacity and the enzyme retained hydrogen peroxide-generating activity. Intradermal administration of the immune conjugate into rats induced local tissue injury at doses 10-100 micrograms. Pronounced damage (local hyperemia and edema) occurred 24 h after injection and necrosis developed 1 week later. The enzyme was tightly bound to the fibrillar components of the extracellular matrix and retained its activity in vivo for a prolonged period of time. In contrast, non-immune IgG-conjugated glucose oxidase was removed rapidly from the site of injection and did not induce tissue damage. Pure native anti-collagen antibody was retained at the site of injection for 8 days, but caused no tissue injury. These results suggest that active glucose oxidase conjugated with antibodies to tissue antigen can be accumulated and retained in the tissues. At the site of accumulation local 'proinflammatory' damage develops even in the absence of the halide-peroxidase system. Similar conjugates could be potential agents for local modulation of inflammation.
Muzykantov
V R
VR
Institute of Experimental Cardiology, U.S.S.R. Cardiology Research Center, Moscow.
Peclo
M M
MM
Printseva OYu
D000818:Animals; D001323:Autoantibodies / Q000633:toxicity*; D003094:Collagen / Q000276:immunology*; D004487:Edema / Q000209:etiology / Q000473:pathology; D005949:Glucose Oxidase / Q000633:toxicity*; D006861:Hydrogen Peroxide / Q000096:biosynthesis; D006940:Hyperemia / Q000209:etiology / Q000473:pathology; D007271:Injections, Intradermal; D008297:Male; D009336:Necrosis; D051381:Rats; D011919:Rats, Inbred Strains; D012867:Skin / Q000201:enzymology / Q000473:pathology*; D013194:Staining and Labeling
D001323:Autoantibodies; D003094:Collagen; D006861:Hydrogen Peroxide; D005949:Glucose Oxidase