title: Differential susceptibility of immune complexes to release from the erythrocyte CR1 receptor by factor I.
abstract: This study was designed to explore the role of Factor I in the release of immune complexes (IC) from human erythrocytes (E). The interactions between E and IC constructed with murine monoclonal antibodies were examined using, as a complement source, autologous plasma, plasma depleted of Factor I by > 90%, or Factor I-depleted plasma reconstituted with purified Factor I. Striking differences were observed in the interactions between E and different types of IC in Factor I-depleted plasma. The release of IC constructed with IgG1, IgG3, IgM or IgA antibodies was abolished by Factor I depletion whereas IC containing IgG2a or IgG2b antibodies were still released from E in Factor I-depleted plasma. Moreover, when IC containing IgG2a antibodies were incubated briefly in Factor I-depleted plasma, under conditions in which the IC were bound but not released, and then resuspended in the presence or absence of Factor I, as little as 5% of the normal physiologic level of Factor I released the IC from E. Thus, IC containing IgG2a antibodies appear to be exquisitely susceptible to release from E by Factor I. Additional differences in the susceptibility of IC containing IgG1, IgG3, IgM or IgA antibodies to release from E were revealed when Factor I-depleted plasma was reconstituted with Factor I. Under these conditions, the relative susceptibility of IC to release was: IC containing IgG1 or IgA antibodies > IC containing IgM antibodies > IC constructed with IgG3 antibodies. While isotype was critical in determining susceptibility to release, some clonotypic differences between isotype-matched pairs of IC were also evident. Differences in IC release from E by Factor I may reflect antibody matrix-mediated differential susceptibility of IC-bound C3b and/or C4b to cleavage by Factor I and may have implications for immunoregulation, host effector cell mechanisms and the pathophysiology of IC diseases.
authors.affiliation: Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City 73190.
authors.forename: I
authors.initials: I
authors.lastname: Yokoyama
authors.forename: F
authors.initials: F
authors.lastname: Waxman
mesh_terms: D000936:Antigen-Antibody Complex / Q000378:metabolism*; D017244:Complement Factor I / Q000172:deficiency / Q000502:physiology*; D004797:Enzyme-Linked Immunosorbent Assay; D004912:Erythrocytes / Q000648:ultrastructure*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D017463:Receptors, Complement 3b / Q000378:metabolism*
chemical_list: D000936:Antigen-Antibody Complex; D007074:Immunoglobulin G; D017463:Receptors, Complement 3b; D017244:Complement Factor I