Fibronectin and serum amyloid P component stimulate C3b- and C3bi-mediated phagocytosis in cultured human monocytes.

Abstract

Receptors for C3 exist in two states, an active state in which the receptors promote phagocytosis and an inactive state in which they do not . For example, cultured human monocytes (MO) bear separate receptors that bind C3b-and C3bi-coated erythrocytes, but neither receptor promotes phagocytosis of such C3-coated erythrocytes (1) . Brief stimulation ofthe MO with the tumor promoter phorbol myristate acetate (PMA), however, renders both C3 receptors competent to generate a phagocytec response . Similarly, C3 receptors of resident murine peritoneal macrophages do not promote phagocytosis but are activated when these cells are incubated with a specific lymphokine (2) . We have been unable to identify a comparable human lymphokine, and therefore sought other molecules that might represent physiological regulators of C3 receptor activity in human mononuclear phagocytes.Recenty, Pommier et al . (3) reported that soluble fibronectin (FN) activates C3b receptors of freshly isolated human monocytes . Other investigators, however, failed to observe this effect (4, 5) . While soluble FN may cause modest activation of C3 receptors on freshly explanted blood monocytes (3), we report here that substrate-bound FN as well as substrate-bound serum amyloid P component (SAP) cause a marked activation of the C3b and the C3bi receptors of MO and that this activation of C3 receptor activity occurs by a novel mechanism : interaction of substrate-bound FN or SAP with the basal portion of the MO plasma membrane activates C3 receptors on the apical portion of the MO plasma membrane . Materials and MethodsReage)its. FN and anti-FN were generous gifts of Dr . M . Furie, The Rockefeller University . FN was purified as described (6), and anti-FN antibodies were raised in a rabbit injected with FN further purified on sodium dodecyl sulfate (SDS) polyacrylamide gels. Purified SAP (7) was a gift of R. Glaviano, Rush Medical College, Chicago . Antibodies against SAP were from Atlantic Antibodies, Scarborough, ME . FN and SAP ran as pure proteins on heavily overloaded SDS polyacrylamide gels. The SAP preparation contained no C-reactive protein detectable by a sensitive radial immunodiffusion procedure .Human serum deficient in complement component C7 (R7) was produced by adsorption on an anti-C7 affinity column as described (8) .

Regulation of macrophage phagocytosis of apoptotic neutrophils by adhesion to fibronectin.

“…Adhesion of macrophages to matrix components may modulate complement receptor function [37,38] and phagocytosis via ␣ 5 ␤ 1 [39]. It is interesting to note that Blystone and colleagues found that binding of fibronectin-coated particles to Fig.…”

Serum Amyloid P Component Binds to Fcγ Receptors and Opsonizes Particles for Phagocytosis

“…Because PMN can ingest unopsonized zymosan through CD11b/ CD18, it was possible that SAP and CRP were providing an activating signal for uptake of zymosan through these receptors (33) rather than directly binding to Fc␥R to promote ingestion of zymosan. Therefore, we also tested the ability of SAP and CRP to opsonize Dynabeads, which are not bound or ingested by PMN in the absence of opsonins (phagocytic and attachment indexes Ͻ10).…”

Altered expression of complement receptors as a pathogenetic factor in systemic lupus erythematosus

“…The biologic function of the receptor probably varies according to the cell type on which it resides. It is involved in endocytic reactions of neutrophils and monocytes (25)(26)(27)(28)(29)(30)(31)(32)(33), and it endows erythrocytes with a potential capacity for adsorbing immune complexes in the circulation (34). Its function on lymphocytes remains largely unknown, although it may enhance response of B cells to other stimulatory factors (35).…”