title: The triggering of fibrinogen receptors on mononuclear phagocytes of healthy subjects and of a thrombasthenia Glanzmann patient promotes the generation of reactive oxygen species.
abstract: The interaction of human fibrinogen (Fg) with homologous mononuclear phagocytes was investigated. Using a radioligand binding test, no evidence for high-affinity binding of either monomeric Fg, of the fibrin fragment E, or of radiolabelled Gly-Pro-Arg-Pro(-Try) to mononuclear phagocytes and myelomonocytic cell lines could be obtained, although commercial labelled Fg specifically bound to monocytes (MO), macrophages (M phi), U937 and HL60 cells. MO pretreated with either commercial or monomeric Fg and washed showed an oxidative burst upon treatment with anti-Fg antibodies, as evidenced by chemiluminescence (CL) measurement in the presence of luminol. The reaction depended on the Fg concentration used for pre-incubation, was divalent cation-independent and was inversely related to the time for which Fg was allowed to dissociate from the cell surface. Induction of the CL response required specific divalent antibodies, but not an intact Fc portion. MO pre-treated with fibronectin (Fn), washed and treated with anti-Fn antibodies exhibited no CL response. MO from a patient with thrombasthenia Glanzmann showed a similar reaction upon pre-incubation with Fg and stimulation with antibody. CL was also triggered by exposure of MO to surface-adsorbed Fg. The response was smaller than that induced by equivalent amounts of IgG, but was larger than that promoted by Fn. Pre-treatment of MO with ADP, fMLP or LPS did not enhance CL induced by surface-adsorbed Fg. Our results suggest that unstimulated mononuclear phagocytes of healthy subjects and of patients lacking the Fg receptors on platelets have receptors that bind the C-gamma-terminus of fibrin(ogen) with relatively low affinity, and that crosslinking of these receptors by surface-bound ligand promotes an oxidative burst but fails to induce cytokine secretion.
authors: Institute of Veterinary Virology, University of Berne, Switzerland.
authors: C
authors: C
authors: Trezzini
authors: L
authors: L
authors: Schalch
authors: T W
authors: TW
authors: Jungi
mesh_terms: D000595:Amino Acid Sequence; D000906:Antibodies; D002478:Cells, Cultured; D016207:Cytokines / Q000032:analysis; D005337:Fibrin / Q000378:metabolism; D005340:Fibrinogen / Q000276:immunology / Q000378:metabolism*; D005353:Fibronectins / Q000378:metabolism; D005609:Free Radicals; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008163:Luminescent Measurements; D008264:Macrophages / Q000378:metabolism*; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000378:metabolism; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism; D010587:Phagocytosis; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism*; D011485:Protein Binding; D015398:Signal Transduction; D013915:Thrombasthenia / Q000097:blood*
chemical_list: D000906:Antibodies; D016207:Cytokines; D005353:Fibronectins; D005609:Free Radicals; D009842:Oligopeptides; D010446:Peptide Fragments; D010980:Platelet Membrane Glycoproteins; C072589:glycyl-prolyl-arginyl-prolyl-tyrosine; D005337:Fibrin; D005340:Fibrinogen; D010100:Oxygen