Complement-mediated clearance of erythrocytes: mechanism and delineation of the regulatory roles of Crry and DAF. Decay-accelerating factor.

Publisher: Elsevier Country of Publication: United States NLM ID: 7603509 Publication Model: Print-Electronic Cited Medium: Print ISSN: 0006-4971 (Print) Linking ISSN: 00064971 NLM ISO Abbreviation: Blood Subsets: MEDLINE

Publication: 2021- : [New York] : Elsevier
Original Publication: New York, Grune & Stratton [etc.]

Erythrocyte Aging* ; Phagocytosis*; CD55 Antigens/*physiology ; Complement C3/*physiology ; Complement Pathway, Alternative/*physiology ; Complement Pathway, Classical/*physiology ; Receptors, Complement/*physiology ; Receptors, IgG/*physiology; Agammaglobulinemia/blood ; Agammaglobulinemia/genetics ; Agammaglobulinemia/immunology ; Anemia, Hemolytic, Autoimmune/blood ; Anemia, Hemolytic, Autoimmune/immunology ; Animals ; Autoantibodies/immunology ; CD55 Antigens/genetics ; Complement C3/deficiency ; Complement C3/genetics ; Complement C4/deficiency ; Complement C4/genetics ; Complement C5/deficiency ; Complement C5/genetics ; Enzyme Activation ; Erythrocyte Transfusion ; Graft Survival ; Hemolysis/physiology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Opsonin Proteins/immunology ; Receptors, Complement/deficiency ; Receptors, Complement/genetics ; Receptors, Complement 3b ; Receptors, IgG/deficiency ; Receptors, IgG/genetics ; Spleen/cytology

The role of complement in the pathogenesis of autoimmune hemolytic anemia (AIHA) has been controversial and may depend on a number of factors, including the affinity and isotype of the pathogenic antibodies involved. We have recently shown that mouse erythrocytes deficient in the membrane C3 regulatory protein, complement receptor 1-related gene/protein y (Crry), but not decay-accelerating factor (DAF), were spontaneously eliminated in vivo by complement. Here, by generating a mouse deficient in both DAF and Crry, we further delineated the roles of Crry and DAF in regulating alternative and classical pathway C3 activation. By using immunoglobulin-, Fcgamma receptor (FcgammaR)-, C3-, C4-, and C5-deficient mice, we also determined the mechanism by which membrane C3 regulator-deficient erythrocytes are cleared from the circulation. Finally, we evaluated the relative importance of the Fc receptor versus the complement pathway in disposing antibody-opsonized DAF/Crry-deficient erythrocytes. We conclude that (1) Crry plays a more dominant role than DAF in regulating the alternative pathway of complement, whereas DAF and Crry are equally effective in preventing antibody-induced runaway complement activation on mouse erythrocytes; (2) DAF/Crry-deficient erythrocytes are eliminated by the alternative pathway of complement via complement receptor-mediated erythrophagocytosis in the spleen; and (3) when opsonized with an immunoglobulin G2a (IgG2a) autoantibody, Crry/DAF-deficient erythrocytes are eliminated more rapidly by complement than by the Fc receptor pathway. These results shed new light on the relative activities of Crry and DAF and underscore the critical roles of membrane C3 regulators in preventing spontaneous and antibody-induced erythrocyte damage in vivo.

AI 40576 United States AI NIAID NIH HHS; AI 44912 United States AI NIAID NIH HHS; AI 44970 United States AI NIAID NIH HHS; AI49344 United States AI NIAID NIH HHS

0 (Autoantibodies)
0 (CD55 Antigens)
0 (Complement C3)
0 (Complement C4)
0 (Complement C5)
0 (Cr1l protein, mouse)
0 (Opsonin Proteins)
0 (Receptors, Complement)
0 (Receptors, Complement 3b)
0 (Receptors, IgG)

Date Created: 20021024 Date Completed: 20030128 Latest Revision: 20210206

20250114

10.1182/blood-2002-06-1875

12393518