Mechanism of transfer of immune complexes from red blood cell CR1 to monocytes.
Complement receptor 1 (CR1) on primate red blood cells (RBC) binds most complement-fixing immune complexes in the circulation. It has been postulated that by binding them, RBC keep immune complexes in the intravascular space and deliver them to the tissue macrophages of the mononuclear phagocyte system. We have developed an in vitro model to study the transfer of RBC-bound immune complexes (heat-aggregated IgG and DNA-anti-DNA) to phagocytic cells (human monocytes). Transfer of immune complexes from RBC to monocytes occurred significantly more rapidly than monocyte uptake of the same immune complexes from solution. In the transfer process, complex-bearing RBC were not bound or sequestered by the monocytes. To define the monocyte receptors involved in binding immune complexes from the RBC surface, monocyte receptors were blocked with MoAbs (anti-CR1, anti-FcRII) or EDTA (to block CR3). Monocyte binding of immune complexes primarily used CR1 with a small contribution from FcRII, and with little or no contribution from CR3 and FcRI. Uptake of immune complexes from solution employed the same monocyte receptors as binding of complexes from the RBC surface. Immune complexes in solution bound to RBC and to monocytes with equally high avidity (approximately 1 x 10(11) l/M), but monocytes expressed a 15-20-fold greater number of immune complex binding sites. We propose that immune complexes distribute between RBC and monocytes according to the binding capacity of these cells, such that at equal or high RBC/monocyte ratios as would be seen in the circulation immune complexes bind to RBC, but at low RBC/monocyte ratios (as would be seen in the sinusoidal circulation of the liver and spleen), most immune complexes bind to monocytes. To define the pathway by which immune complexes move from RBC to monocytes, their release from RBC CR1 was examined. Under various conditions, the dissociation rate was extremely slow, and did not increase with the addition of monocyte supernatants. To examine whether factor I-mediated processing of immune complexes enhances binding of immune complexes to monocytes, RBC-bound complexes were released with factor I, and binding of these 'processed' immune complexes to monocytes was examined. Monocyte binding of these processed immune complexes was slower than of control ones; furthermore, performance of transfer experiments at 4 degrees C, which significantly shows enzymatic processes, did not decrease the rate of immune complex transfer from RBC to monocytes.(ABSTRACT TRUNCATED AT 400 WORDS)
Emlen
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Division of Rheumatology, University of Colorado Health Sciences Center, Denver 80262.
Carl
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V
Burdick
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D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex / Q000276:immunology*; D015703:Antigens, CD / Q000276:immunology; D001665:Binding Sites / Q000502:physiology; D003080:Cold Temperature; D004247:DNA / Q000276:immunology; D004912:Erythrocytes / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D066298:In Vitro Techniques; D009000:Monocytes / Q000276:immunology*; D010587:Phagocytosis / Q000502:physiology*; D011951:Receptors, Complement / Q000276:immunology*; D017463:Receptors, Complement 3b; D017452:Receptors, IgG; D013997:Time Factors
D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D015703:Antigens, CD; D007074:Immunoglobulin G; D011951:Receptors, Complement; D017463:Receptors, Complement 3b; D017452:Receptors, IgG; D004247:DNA