Local opsonization by secreted macrophage complement components. Role of receptors for complement in uptake of zymosan.

Abstract

Circulating monocytes and tissue macrophages (Me) 1 secrete complement proteins and have distinct receptors for some of these secreted products. Although hepatocytes and possibly epithelial cells are major sources of plasma complement (1), Mcl synthesize C1 subcomponents (2, 3), C4 (4, 5), C2 (5-7) C5 (8), C3 (2, 8) and all the components of the alternative pathway and its control proteins (8). Current evidence indicates that M~ bear at least two distinct receptors for fragments of activated C3 (9, 10). The type one complement receptor, CR1 (205 kD) displays specificity for activated C3 (C3b) (11) and C4 (C4b) (12). CR 1 interacts with iC3b, the product of C3b cleavage by factor I (9), although anti-CR 1 antibodies that block C3b-dependent rosetting do not block iC3b-dependent rosetting (13,14). The type three complement receptor, CR3, (170 and 95 kD) interacts with iC3b, and possibly with the further degradation product C3dg (9).In order to investigate the physiological role of M¢ complement products we made use of monoclonal antibodies (ab) that are specific for CR1 (13) and that recognize epitopes associated with CR3 (15, 16). We found that deposition of M~-derived C3 on the acceptor surface of zymosan particles mediated binding and ingestion of zymosan via M~ CR3. Zymosan uptake could also be mediated via mannosyl, fucosyl receptors (MFR, 17) in those M~ populations that possess both CR3 and MFR activity (18). These studies indicate a role for M~ complement in local opsonization and host defense. Materials and Methods AnimalsSwiss outbred (PO) and CBAT6T6 and C57bl mice were bred at the Sir William Dunn School of Pathology, Oxford, and both sexes used at 20-30 g.

Syk‐dependent ERK activation regulates IL‐2 and IL‐10 production by DC stimulated with zymosan

“…The clarity of Syk dependence versus MyD88 dependence of zymosan-induced ERK activation observed here is in many ways surprising, given both the complexity of zymosan as a stimulus [9] and the number of receptors potentially involved in zymosan recognition [10][11][12][13][14][15][16][17][18][19]. This suggests that zymosan may prove to be a useful, simplified model of whole pathogenic yeasts, with which to dissect innate fungal recognition.…”

“…A large number of receptors have been implicated in the recognition of zymosan by murine DC and macrophages, including SIGNR1 [10], mannose receptor [11][12][13][14][15], complement receptor 3 [13][14][15][16][17], dectin-1 [18] ad TLR2/6 [19]. The role of some of these has previously been studied in the context of an atypical cytokine response from zymosan-stimulated DC, characterised by high levels of IL-2 and IL-10, and relatively low levels of IL-12 p70 [20,21].…”

Fc gamma receptor IIIb enhances Fc gamma receptor IIa function in an oxidant-dependent and allele-sensitive manner.

“…that stimulated PMN might release the complement component C3, which becomes activated and bound to the erythrocyte probe ("auto-opsonization") (31,32). Pretreatment (38,39).…”

Superoxide Anion Generation in Human Milk Macrophages: Opsonin-Dependent Versus Opsonin-Independent Stimulation Compared with Blood Monocytes

“…Monocytes and MM⌽ have been shown to secrete essential factors for activation and propagation of the alternative complement pathway (1,34), so they are capable of local zymosan opsonization via autocrine liberation of complement factors (35,36).…”