Increased Leukocyte Thromboplastin Activity by Sensitized Lymphocytes: A Link Between Immunology and Blood Coagulation

Abstract

Fibrin deposition and infiltration of mononuclear leukocytes (MN) frequently occurs concomitantly at the site of an immune reaction. As human MN can produce thromboplastin (TP) we have investigated whether immune stimulation of MN can trigger the production of TP by these cells. Both specific antigen (tuberculin PPD) and allogeneic lymphocytes were used for stimulation. MN from 14 donors with a high response to PPD and from 11 donors with a low response to PPD (based on the incorporation of 3H-thymidine) were cultured for 7 days in the presence or absence of PPD and the TP activity of the whole cell suspension was determined. When PPD was absent, TP levels in MN from low and high responders were not different (113±47 and 197±111 u/ml resp. p ˃ 0.10). With PPD, however, MN from high responders produced 1470±413 u TP/ml compared to 126±49 u TP/ml produced by MN from low responders (p < 0.005). Similar results were obtained when MN were kept in culture for either 4 or 11 days. However, after 24 hours in culture, TP synthesis was not different in the MN of the 2 groups. When MN were cultured in a mixed leukocyte reaction, allogeneic MN produced more TP (405±151 u/ml) than control cultures (95±21 u/ml) (p<0.025;n=22). These data indicate that stimulated lymphocytes can enhance TP activity of leukocytes. It is postulated that fibrin formation in immune reactions such as delayed hypersensitivity and rejection of kidney allografts is mediated by immunologically stimulated MN.