title: Inhibition by monoclonal anticomplement receptor type 1 on interactions between senescent human red blood cells and monocytic-macrophagic cells.
abstract: The effect of different murine monoclonal antibodies (Mab) specific for the glycoprotein complement receptor type 1 (CR1), type 2 (CR2), and type 3 (CR3) on the adhesion to and on the phagocytosis of human senescent red blood cells (S-RBC) by monocytes or by monocyte-derived macrophages (M phi) was investigated. Murine Mab anti-CR3 (anti-Leu 15 and OKM1) were found to inhibit, in the same order of magnitude, on one hand, the Fc receptors (FcR)-dependent rosetting and phagocytosis, and, on the other hand, the S-RBC rosetting and phagocytosis by adherent monocytes. Thus, the specific involvement of the CR3 epitopes recognized by Mab anti-Leu 15 or by OKM1 in the interactions between S-RBC and monocyte/macrophage could not be demonstrated. Murine Mab anti-CR1 was found to be a significant inhibitor of binding to and of phagocytosis of S-RBC (but not of young [Y] RBC) by monocytes or M phi, whereas Mab OKM5 carrying the same isotype as Mab anti-CR1, but a different specificity, was devoid of any significant inhibitory effect. Furthermore, Y-RBC or S-RBC opsonized with Mab anti-CR1 did not form FcR-dependent rosettes and were not internalized by monocytes; in addition, preincubation of phagocytes with Mab anti-CR1 did not inhibit FcR-dependent rosetting and phagocytosis. These results suggest that the effect of anti-CR1 is mediated through a specific binding to CR1 and not through an FcR blockade. As the role of specifically bound IgG on phagocytosis of human S-RBC by macrophages has previously been demonstrated by several authors, the present study suggests that monocyte-macrophage complement receptor type 1 may act in synergy with Fc receptors in the recognition of S-RBC by macrophages. It is shown in addition that the tripeptide Arg-Gly-Asp, identical to the region of iC3b recognized by CR3 and by several adhesion-promoting receptors that are structurally similar to CR3, such as fibronectin or vitronectin, is a significant inhibitor of the binding to and the phagocytosis of S-RBC by monocytic-macrophagic cells.
authors.affiliation: Laboratoire de Biologie Cellulaire, Université Paris XIII, Bobigny, France.
authors.forename: L
authors.initials: L
authors.lastname: Gattegno
authors.forename: L
authors.initials: L
authors.lastname: Saffar
authors.forename: J
authors.initials: J
authors.lastname: Vaysse
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D002448:Cell Adhesion; D002469:Cell Separation; D004905:Erythrocyte Aging; D004912:Erythrocytes / Q000276:immunology*; D006801:Humans; D066298:In Vitro Techniques; D008264:Macrophages / Q000276:immunology*; D009000:Monocytes / Q000276:immunology*; D009842:Oligopeptides / Q000494:pharmacology; D010587:Phagocytosis; D011951:Receptors, Complement / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D009842:Oligopeptides; D011951:Receptors, Complement; C047981:arginyl-glycyl-aspartic acid