Effect of insulin immune complexes on human blood monocyte and endothelial cell procoagulant activity.
Insulin antibodies and immune complexes (ICs) are present in most patients with diabetes after initiation of conventional insulin therapy. We studied the ability of bovine insulin, porcine insulin, and human insulin ICs to stimulate the procoagulant activity (PCA) of human blood monocytes (HBMs) and human umbilical vein endothelium (HUVE) in vitro. Polyclonal insulin antibodies from patients with insulin antibody-mediated resistance were isolated by immunoabsorption. PCA expressed by isolated adherent HBMs or cultured HUVE was quantified by radioimmunoassay of fibrinopeptide A with a 1:80 dilution of human plasma. Beef, pork, and human insulin, in quantities determined from titration curves, were added to fixed amounts of antibody to obtain equivalent amounts of ICs. For four different antibodies, the ratios of PCA (expressed by HBMs exposed to ICs or to antibodies alone and normalized for cell numbers) to activity expressed by tissue culture medium were as follows: beef insulin ICs, 2.55 +/- 0.41; por insulin ICs, 1.47 +/- 0.16; human insulin ICs, 1.28 +/- 0.19; and antibody, 1.28 +/- 0.32. The differences between beef and pork insulin ICs and antibody controls were significant. For a fifth antibody, a dose response between beef insulin ICs and PCA expression was demonstrated. For a sixth antibody, HBMs could express PCA when stimulated with antibody of a relatively low binding capacity (0.35 ng bovine insulin per microgram of antibody) only in the presence of lymphocytes. Conditioned medium from these cells significantly stimulated endothelial cell procoagulant activity. These observations raise the possibility that insulin ICs, that is, beef insulin ICs, may generate increased PCA and thereby contribute to the vascular complications of diabetes mellitus.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D000936:Antigen-Antibody Complex / Q000276:immunology*; D001779:Blood Coagulation Factors / Q000096:biosynthesis*; D002417:Cattle; D003925:Diabetic Angiopathies / Q000209:etiology; D004730:Endothelium, Vascular / Q000378:metabolism*; D005344:Fibrinopeptide A / Q000032:analysis; D006801:Humans; D007328:Insulin / Q000276:immunology*; D009000:Monocytes / Q000378:metabolism*; D013552:Swine; D013925:Thromboplastin / Q000096:biosynthesis*
D000936:Antigen-Antibody Complex; D001779:Blood Coagulation Factors; D007328:Insulin; C045071:leukocyte procoagulant activity; D005344:Fibrinopeptide A; D013925:Thromboplastin