Processing of C3b-opsonized immune complexes bound to non-complement receptor 1 (CR1) sites on red cells: phagocytosis, transfer, and associations with CR1.
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.
Craig
Maria L
ML
Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA 22908, USA.
Waitumbi
John N
JN
Taylor
Ronald P
RP
D000911:Antibodies, Monoclonal / Q000378:metabolism; D000936:Antigen-Antibody Complex / Q000097:blood / Q000378:metabolism*; D001666:Binding Sites, Antibody; D018958:CD55 Antigens / Q000378:metabolism; D045744:Cell Line, Tumor; D003179:Complement C3b / Q000276:immunology / Q000378:metabolism*; D004910:Erythrocyte Membrane / Q000276:immunology / Q000378:metabolism*; D006021:Glycophorins / Q000276:immunology / Q000378:metabolism; D006801:Humans; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D009895:Opsonin Proteins / Q000097:blood / Q000378:metabolism*; D010587:Phagocytosis / Q000276:immunology*; D011485:Protein Binding / Q000276:immunology; D011499:Protein Processing, Post-Translational / Q000276:immunology*; D021381:Protein Transport / Q000276:immunology; D017463:Receptors, Complement 3b / Q000097:blood / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D018958:CD55 Antigens; D006021:Glycophorins; D009895:Opsonin Proteins; D017463:Receptors, Complement 3b; D003179:Complement C3b