Rothberger H, Zimmerman T S, Spiegelberg H L, Vaughan J H
J Clin Invest. 1977 Mar;59(3):549-57. doi: 10.1172/JCI108670.
In a variety of immunologic diseases, fibrin-fibrinogen and immune complexes deposit in areas of tissue damage. However, the mechanisms which initiate fibrin-fibrinogen deposition have not been clarified. We find that the procoagulant activity of human leukocytes is markedly increased after incubation with immunoglobulin and immune complexes. This procoagulant activity is evident after 4-24 h incubation in the presence of as little as 0.1 mg/ml of autologous, isologous, or heterologous IgG. At least three of the four subclasses of IgG myeloma proteins are effective. Experiments with purified rabbit and rat antibodies demonstrate that enhancement of procoagulant activity is significantly greater with soluble antigen-antibody complexes than with immunoglobulin alone. In contrast, insoluble complexes are less affective than immunoglobulin alone. Artifacts due to endotoxin contamination of the IgG preparations were excluded on the basis of the differential sensitivities of immunoglobulin and endotoxin to heat and polymyxin B. Evidence is also presented which shows that enhancement of procoagulant activity involves the production, rather than a simple release, of leukocyte procoagulant activity in vitro.
在多种免疫疾病中,纤维蛋白 - 纤维蛋白原和免疫复合物沉积于组织损伤部位。然而,引发纤维蛋白 - 纤维蛋白原沉积的机制尚未阐明。我们发现,人白细胞与免疫球蛋白及免疫复合物孵育后,其促凝活性显著增强。在存在低至0.1mg/ml的自体、同种或异种IgG的情况下,孵育4 - 24小时后,这种促凝活性就很明显。IgG骨髓瘤蛋白的四个亚类中至少有三个是有效的。用纯化的兔和大鼠抗体进行的实验表明,可溶性抗原 - 抗体复合物比单独的免疫球蛋白更能显著增强促凝活性。相比之下,不溶性复合物的效果比单独的免疫球蛋白更差。基于免疫球蛋白和内毒素对热和多粘菌素B的不同敏感性,排除了IgG制剂受内毒素污染产生的假象。还有证据表明,促凝活性的增强涉及体外白细胞促凝活性的产生,而非简单的释放。