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Processing of C3b-Opsonized Immune Complexes Bound to Non-Complement Receptor 1 (CR1) Sites on Red Cells: Phagocytosis, Transfer, and Associations with CR1¹

Maria L. Craig^*, John N. Waitumbi and Ronald P. Taylor^2,*

^* Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA 22908; and U.S. Army Medical Research Unit and Kenya Medical Research Institute, Nairobi, Kenya

Severe anemia is a lethal complication of Plasmodium falciparum malaria, particularly in children. Recent studies in children with severe P. falciparum anemia have demonstrated elevated levels of E-bound Abs, reduced E-associated complement receptor 1 (CR1) and decay-accelerating factor (DAF), and pronounced splenic enlargement, suggesting a mechanism for E loss involving Abs, complement, and phagocytosis. Motivated by these reports, we have developed an in vitro model in which human E with Abs and complement bound to CR1, DAF, or glycophorin A are incubated with model human macrophages (the THP-1 cell line). Previous work has demonstrated that immune complex (IC) substrates bound to E CR1, either by an Ab or via C3b, are transferred to macrophages with loss of CR1. In this study, we report that IC bound to DAF or glycophorin A by an Ab linkage are also transferred to macrophages. DAF is lost from the E during the transfer of DAF-bound IC, but the transfer of CR1-bound IC does not lead to a significant loss of DAF. Using glycophorin A-bound IC, we observe competition between transfer of IC and phagocytosis of the E: a fraction (15%) of the E was phagocytosed, while the remaining E were stripped of IC. We also examined the organization of CR1 and DAF in the presence of E-bound Ab/complement. We find that CR1, but not DAF, colocalizes with IgM mAb-C3b and IC-C3b substrates attached to glycophorin A. We observe that the binding of the IgM mAb-C3b to glycophorin A induces a novel unclustering of CR1.

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