Immune complex erythrocyte complement receptor interactions in vivo during induction of glomerulonephritis in nonhuman primates
- Ohio State Univ. Hospitals, Columbus (USA)
Multiple lines of evidence indicate that the erythrocyte complement receptor (E-CR) system, which is unique to the primate, may play an important role in the clearing of immune complexes (ICs) from the circulation. However, all previous investigations of IC/E-CR interactions in vivo have involved the study of small amounts of preformed or passively formed ICs interacting with E-CR that were numerically in vast excess. The present study was undertaken to assess IC/E-CR interactions under conditions in which large amounts of ICs were formed in the circulation, amounts that when sustained for several weeks by daily intravenous administration of antigen resulted in the development of active glomerulonephritis. Twelve cynomolgus monkeys with E-CR levels ranging from 25 to 5000 mean CRs per erythrocyte (CR/E) were actively immunized to BGG, and 6 to 12 weeks later they were studied first at low levels of IC formation in vivo and then at high levels of IC formation in vivo (H-Protocol experiments, mean 125I-labeled BGG dose 4.9 mg/kg given over 10 minutes, a state approximating antigen-antibody equivalence). Cynomolgus monkeys with fewer than 100 CR/E showed no evidence of binding of ICs to erythrocytes with either low-dose or high-dose 125I-labeled BGG. However, cynomolgus monkeys with greater than 450 CR/E showed significant binding of ICs to erythrocytes: mean peak binding of 125I-labeled BGG to erythrocytes was 22.1% +/- 1.1% in the L-Protocol experiments and 33.4% +/- 8.0% in the H-Protocol experiments. During H-Protocol experiments, mean CR/E, measured by using a monoclonal anti-human CR1 antibody, decreased acutely, with recovery of E-CR levels within the next 24 to 72 hours. The acute decrease in E-CR levels could not be accounted for by occupancy of E-CR by ICs or by change in hematocrit.
- OSTI ID:
- 6511587
- Journal Information:
- Journal of Laboratory and Clinical Medicine; (USA), Vol. 116:2; ISSN 0022-2143
- Country of Publication:
- United States
- Language:
- English
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