Complement receptor type 3 (CR3) binds to an Arg-Gly-Asp-containing region of the major surface glycoprotein, gp63, of Leishmania promastigotes.

Abstract

Leishmania is an obligate intracellular parasite that survives within the phagolysosomes ofits vertebrate hosts' macrophages (1-3). Once the promastigote form ofthe parasite is introduced into the host tissue by a feeding sandfly, it must gain entry into a macrophage in order to survive and develop into the amastigote form. The initial attachment of Leishmania promastigotes to the macrophage is receptor mediated (4-6), however, the identity ofthe ligands on the parasite and their complementary receptors on the surface of the phagocyte is not known. Since some receptors on the macrophage surface initiate a microbicidal response when complexed with their ligand, and others do not (7-9), one possible means by which the parasite may increase its chance of successfully infecting the macrophage is in the "choice" of receptor(s) used during phagocytosis .To date, two ligands on the surface of the promastigote capable of independently mediating attachment to the macrophage surface have been identified and isolated. These are the promastigote surface glycoprotein gp63 (10) and the promastigote lipophosphoglycan (11). The receptors for these specific ligands have not as yet been identified, but several studies conducted on intact parasites have implicated a variety of receptors that may function in the binding ofpromastigotes to macrophages. These receptors include the mannosyl/fucosyl receptor (5), a receptor for nonenzymatically glucosylated moeities (12), and the complement receptor type 3 (CR3) (13-15). Paradoxically, CR3 recognizes Leishmania promastigotes in the absence ofexogenous complement . This led to the proposal that the macrophages itself secretes complement components that then deposit on the promastigote surface (13,14). In the present study, we demonstrate that CR3 is the receptor for the promastigote surface glycoprotein gp63 and that CR3 binds directly to a region of gp63 containing the amino acid sequence Arg-Gly-Asp

The distinct leukocyte integrins of mouse spleen dendritic cells as identified with new hamster monoclonal antibodies.

“…CD11a contributes to the homotypic binding of lymphocytes (21), and to the heterotypic binding of T to B cells (8) and of CTL to their targets (3). CD11b mediates the adhesion of phagocytes to particles opsonized with C3bi (28) and other ligands (34)(35)(36), and to endothelium (37).…”

Transcriptional Inhibition of Interleukin-12 Promoter Activity in Leishmania Spp.–Infected Macrophages

“…parasites with normal mouse serum is not necessary for inhibition (data not shown), suggesting that CR3 ligation is not mediating the interaction. However, MP are able to synthesize complement components (McPhaden and Whaley, 1993) that opsonize parasites even in serum-free conditions (Wozencraft et al, 1986) and parasite components have been suggested to bind CR3 directly (Russell and Wright, 1988;Talamas-Rohana et al, 1990;Kedzierski et al, 2004). Furthermore, the repetitive structure and glycan modifications associated with many Leishmania spp.…”

Subversion of Innate Immunity by Periodontopathic Bacteria via Exploitation of Complement Receptor-3

“…This receptor recognizes a wide variety of structurally unrelated molecules from either the host (e.g., complement C3 fragment [iC3b], intercellular adhesion molecule-1 [ICAM-1], or fibrinogen) or pathogens (e.g., Bordetella pertussis filamentous hemagglutinin and Leishmania gp63) (Diamond et al, 1993;McGuirk and Mills, 2000;Russell and Wright, 1988). Similarly to other integrins, CR3 integrates the intracellular and extracellular environments through inside-out and outside-in bidirectional signaling.…”