Immune complex erythrocyte complement receptor interactions in vivo during induction of glomerulonephritis in nonhuman primates

Daniel J. Birmingham, Lee A. Hebert, Fernando G. Cosio, Michael E. VanAman

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21 Scopus citations

Abstract

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 glomerulonephrittis. Twelve cynomolgus monkeys with E-CR levels ranging from 25 to 5000 mean CRs per eryrthrocyte (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 (L-Protocol experiments, mean 125l-labeled BGG dose of 0.04 mg/Kg given over 1 minute, a marked antibody excess state) and then at high levels of IC formation in vivo (H-Protocol experiments, mean 125l-labeled BGG dose 4.9 mg/kg given over 10 minutes, a state approximating antigen-antibody equivalence). Cynomoigus monkeys with fewer than 100 CR/E showed no evidence of binding of ICs to erythrocytes with either low-dose or high-dose 125l-labeled BGG. However, cynomolgus monkeys with greater than 450 CR/E snowed significant binding of ICs to erythrocytes: mean peak binding of125l-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 (mean decrease 36.2% ± 14.1%, p < 0.05), 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. In summary, the present study demonstrates that during the development of glomerulonephritls, IC/E-CR interactions occur and the E-CR system is altered by these interactions. The present observations are consistent with the hypothesis that the E-CR system may play a role in the pathogenesis of IC-mediated disease in the primate.

Original languageEnglish (US)
Pages (from-to)242-252
Number of pages11
JournalThe Journal of Laboratory and Clinical Medicine
Volume116
Issue number2
StatePublished - Aug 1990

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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