Plasma lipoprotein induction and suppression of the generation of cellular procoagulant activity in vitro.
Isolated human plasma very low density, intermediate density, and high density lipo-proteins at physiologic concentrations have been demonstrated in the preceding report to induce significant increases in the procoagulant activity of human peripheral blood mononuclear cells in vitro, whereas low density lipoprotein did not. The monocyte was identified in this study by cellular fractionation and by direct cytologic assays as the source of this inducible activity, thus identifying the procoagulant activity as a monokine. The generation of these lipoprotein-induced procoagulant monokines was entirely dependent upon the presence of lymphocytes. Isolated lymphocytes that had been exposed to the stimulatory lipoproteins could induce monocytes to produce the procoagulant activity, whereas neither the culture medium from lipoprotein-stimulated lymphocytes, homogenates of lymphocytes, nor other cells such as platelets could substitute for this requirement. The interaction of the stimulatory lipoproteins with lymphocytes was rapid, reaching completion within 30 min, and was equally effective at either 4 degrees or 37 degrees C. Low density lipoprotein did not stimulate lymphocytes to induce monocyte procoagulant activity, but did actively suppress the production of the procoagulant monokines induced by each of the stimulatory lipoproteins, as well as bacterial lipopolysaccharide. The monocyte was identified as the cell sensitive to low density lipoprotein suppression, and no suppression of lymphocyte triggering was observed. These observations on the interaction of plasma lipoproteins with lymphocytes and monocytes in vitro introduce two new regulatory events by which plasma lipoproteins influence the function of cells, and define a regulatory network by which certain lipoprotein classes trigger lymphocytes, which can in turn induce monocytes to express procoagulant activity. Only this latter phase is subject to lipoprotein suppression by physiologic concentrations of low density lipoprotein.
D001779:Blood Coagulation Factors / Q000096:biosynthesis*; D002450:Cell Communication / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D008070:Lipopolysaccharides / Q000494:pharmacology; D008074:Lipoproteins / Q000378:metabolism / Q000494:pharmacology*; D008077:Lipoproteins, LDL / Q000494:pharmacology; D008214:Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism
D001779:Blood Coagulation Factors; D008070:Lipopolysaccharides; D008074:Lipoproteins; D008077:Lipoproteins, LDL