Concurrent production of macrophage agglutination factor and factor VII by antigen-stimulated human peripheral blood mononuclear cells.
We have studied concurrent production of macrophage agglutination factor (MAggF) and procoagulant activity by antigen-stimulated human blood mononuclear cells to gain insight into biochemical mechanisms underlying delayed hypersensitivity inflammatory reactions. After stimulation of cells from tuberculin-sensitive donors with tuberculin, MAggF was present in culture supernatants while the overwhelming majority of procoagulant activity remained cell-associated. Neither MAggF nor procoagulant activity was found in reconstituted control cultures, nor in tuberculin-stimulated cultures of non-sensitive cells. Concanavalin A and lipopolysaccharide elicited both activities from cultured mononuclear cells, regardless of donor sensitivity. Human MAggF bound to insolubilized gelatin, heparin and a monoclonal anti-fibronectin (FN) antibody, and its activity was inhibited by another monoclonal antibody directed against the gelatin-binding domain of FN. Treatment of indicator peritoneal exudate cells with monoclonal anti-FN receptor antibody inhibited their response to human MAggF. These results suggest that human MAggF, like the analogous guinea-pig activity, is FN-associated. Antigen-elicited procoagulant activity shortened the recalcification time of normal, factor VII- and factor IX-deficient plasma, partially corrected prothrombin times of factor VII-deficient plasma, had no effect on recalcification and prothrombin items of factor X- and factor V-deficient plasma, and was inhibited by specific anti-factor VII antibody. Thus, human mononuclear cell procoagulant consists of both tissue factor and factor VII, whether it is induced by antigen or mitogen. Antigen-stimulated blood mononuclear cells are able to provide a signal for local fibrin deposition and a protein mediating fibrin binding to mononuclear phagocytes and collagen at sites of delayed hypersensitivity reactions.
D000818:Animals; D000941:Antigens / Q000276:immunology; D002449:Cell Aggregation / Q000187:drug effects; D002478:Cells, Cultured; D003208:Concanavalin A / Q000494:pharmacology; D005167:Factor VII / Q000096:biosynthesis*; D005353:Fibronectins / Q000276:immunology; D005780:Gelatin; D006168:Guinea Pigs; D006493:Heparin; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007962:Leukocytes / Q000276:immunology / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008222:Lymphokines / Q000096:biosynthesis*; D008264:Macrophages / Q000276:immunology; D017469:Receptors, Fibronectin; D011971:Receptors, Immunologic / Q000276:immunology; D012882:Skin Tests; D014373:Tuberculin
D000941:Antigens; D005353:Fibronectins; D008070:Lipopolysaccharides; D008222:Lymphokines; D017469:Receptors, Fibronectin; D011971:Receptors, Immunologic; D014373:Tuberculin; C035408:macrophage aggregation factor; D003208:Concanavalin A; D005780:Gelatin; D005167:Factor VII; D006493:Heparin