Leukocyte procoagulant activity: enhancement of production in vitro by IgG and antigen-antibody complexes

Abstract

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.