Fibronectin receptors of phagocytes. Characterization of the Arg-Gly-Asp binding proteins of human monocytes and polymorphonuclear leukocytes.

Abstract

We have defined the cell surface molecules of human monocytes and PMN that bind to the chymotryptic cell binding domain of Fn and to a synthetic peptide, KYAVTGRGDS, based on the sequence of Fn, by affinity chromatography. Monocytes express two receptors that differ in their affinity for CBD-Sepharose and peptide-Sepharose, but that both recognize the RGD sequence. Only a single receptor is purified from PMN, which resembles the monocyte surface molecule that binds to peptide-Sepharose. These receptors are not part of the Mac-1, LFA-1, p(150,95) family, but do have homology to the platelet Fn receptor, gpIIb/IIIa. Interestingly, the antigenic crossreactivity between gpIIb/IIIa and the phagocyte receptors purified on peptide-Sepharose is largely in the beta chain of the receptors. The alpha chains appear to be distinct, based on molecular weight, antigenic analysis, and ligand specificity. This receptor also seems to be the surface molecule on monocytes that is critical for phagocytosis enhancement by Fn. Thus, we have defined the phagocyte Fn receptor that transduces the signal for increased phagocytosis by monocytes; it may be a third member of a family of adhesion molecules that includes the gpIIb/IIIa of platelets and the vitronectin receptor of fibroblasts.

Integrin alpha v beta 3 differentially regulates adhesive and phagocytic functions of the fibronectin receptor alpha 5 beta 1.

“…Receptor expression on macrophages and K562 cells was analyzed by fluorescent flow cytometry as described (13,43).…”

“…In addition, macrophage adhesion to fibronectin-coated surfaces affects a variety of macrophage functions including chemotaxis (25, 50), differentiation (8), secretion (7,45), and phagocytosis via immunologic receptors (12,52,66). Nonetheless, the moleculax nature of the interactions leading to these critical macrophage functions is unknown.Studies which have examined fibronectin receptors on macrophages in detail have demonstrated an unexpectedly large number of integrin and non-integrin fibronectin-binding proteins (10,13,16,17,29,42,59,63). Four integrin receptors with fibronectin binding capability have been identified on mononuclear phagocytes.…”

“…Studies which have examined fibronectin receptors on macrophages in detail have demonstrated an unexpectedly large number of integrin and non-integrin fibronectin-binding proteins (10,13,16,17,29,42,59,63). Four integrin receptors with fibronectin binding capability have been identified on mononuclear phagocytes.…”

“…Four integrin receptors with fibronectin binding capability have been identified on mononuclear phagocytes. Fibronectin binding to VLA-5 (ot5/~1), the vitronectin receptor (otJ~3) and the Leukocyte Response Integrin (LRI) appears dependent on the RGD adhesion sequence (13,16,29); (VLA-4 (~,) binds fibronectin independent of this sequence (28). Additional macrophage integrins ~J~5, VLA-3 (ot3/~,), and OtM/~2, may also bind fibronectin (1%42, 59,63).…”

Identification and characterization of opsonic fibronectin in synovial fluids of patients with active rheumatoid arthritis

“…Taken together, the findings indicate that the novel fibronectin fragments with opsonic activity for particulate activators are generated by cleavage from the amino-terminus. As with the gelatin binding plasma-derived fragment, 180K-opFnf (12), the synovial fluid fibronectin fragments with the BD4 epitope were opsonic via binding to the target particles (Figure 7), to provide a link to the fibronectin receptors on monocytes (12, [21][22][23]. The opsonic domain is the functional determinant that permits 180K-opFnf to distinguish asialylated microbial and sialic acid-deficient erythroid particulate activators (E') from fully sialylated nonactivators such as Es (24), and then provides the domain for interaction with the monocyte (12).…”