Specificity of Membrane Complement Receptor Type Three (CR3) for ß-Glucans

Abstract

The binding of the iC3b receptor (CR3) to unopsonized zymosan was shown to result from CR3 attachment to cell wall ß-glucans. A specificity of neutrophil responses for ß-glucan was first suggested by a comparison of yeast (Saccharomyces cerevisiae) cell wall components for stimulation of a neutrophil superoxide burst. Neutrophils responded poorly to heat-killed yeast, but gave increasingly better responses to cell wall polysaccharides devoid of proteins (zymosan) and nearly pure ß-glucan particles derived from zymosan. Zymosan triggered a burst that was 29% as great as that stimulated by phorbol myristate acetate (PMA), and ß-glucan particles stimulated a burst that was 72% as great as that produced by PMA. Phagocytic responses to yeast were also inhibited by soluble glucans but not by soluble mannans. Three types of experiments demonstrated a role for CR3 in these responses. First, neutrophil ingestion of either yeast or yeast-derived ß-glucan particles was blocked by monoclonal anti-CR3, fluid-phase iC3b, or soluble ß-glucan from barley. Monocyte ingestion of ß-glucan particles was also blocked by anti-CR3, but not by anti-CRi or anti-C3. Second, the neutrophil superoxide burst response to either zymosan or ß-glucan particles was blocked by anti-CR3 or fluid-phase iC3b, and was completely absent with neutrophils from 3 patients with an inherited deficiency of CR3. Third, CR3 was isolated from solubilized neutrophils by affinity chromatography on ß-glucan-Sepharose.

Activation of rat macrophages by Betafectin PGG-glucan requires cross-linking of membrane receptors distinct from complement receptor three (CR3)

“…Ross et al [46,48,52,53] have recently provided evidence that the human CR3 (CD11b/CD18) receptor contains a binding site that interacts with both soluble and particulate (1,3)-␤-glucans. We next examined whether PGG-glucan may be mediating its biological effects via the rat CR3 receptor.…”

CD8– dendritic cells preferentially cross‐present Saccharomyces cerevisiae antigens

“…In addition to dectin-1 and TLR2, complement receptors such as CR3 have also been shown to bind directly to non-opsonized zymosan via their lectin domains [27,28]. In addition, SIGNR1 [29] and the mannose-receptor (MR) can also bind fungal components, but these receptors are mainly expressed by macrophages [11,30,31].…”

“…Signaling through an immunoreceptor tyrosinebased activation motif (ITAM)-like motif allows dectin-1 to generate inflammatory responses in addition to its role as a phagocytosis receptor. Ligand binding results in phosphorylation of the ITAM motif, leading to the activation of the downstream tyrosine kinase Syk, CARD9 and initiation of phagocytosis, respiratory burst and production of the cytokines IL-2 and 26].In addition to dectin-1 and TLR2, complement receptors such as CR3 have also been shown to bind directly to non-opsonized zymosan via their lectin domains [27,28]. In addition, SIGNR1 [29] and the mannose-receptor (MR) can also bind fungal components, but these receptors are mainly expressed by macrophages [11,30,31].…”

Effect of iC3b binding to immune complexes upon the phagocytic response of human neutrophils: synergistic functions between FcγR and CR3

“…CR3 (CD1 lb/CD18) is a member of integrin lamily and is responsible for the binding and phagocytosis of iC3b-opsonized IC, although signals through CR3 alone are 19o weak to induce a significant phagocytic response in resting l~eutrophils [5]. In addition to the iC3b-binding domain, CR3 ~n neutrophils has a lectin-like domain through which it also ~ cts as a pluripotent receptor in the recognition of zymosan [6], / -glucan [7], and Escherichia coli [8].…”