The kinetics and metabolic requirements for direct lymphocyte induction of human procoagulant monokines by bacterial lipopolysaccharide.

Human peripheral blood mononuclear cells generate procoagulant activity (PCA), consistent with tissue factor, upon exposure to bacterial lipopolysaccharide (LPS). This is expressed by viable cells and is not secreted in an active form to a significant degree. Monocytes as a class are demonstrated directly to be the cellular source of the LPS-stimulated procoagulant activity; however, direct lymphocyte collaboration is required for the rapid induction of PCA expression. In contrast, platelets were unable to collaborate in the induction of monocyte PCA. When lymphocytes were separated into T-enriched and T-depleted fractions by cytoadherence to neuraminidasetreated sheep erythrocytes only the LPS-triggered T-enriched cells induced monocyte PCA, and full induction of activity was observed. This pathway appeared unidirectional in that lymphocytes alone, after 30-min exposure to LPS, were fully capable of inducing most monocytes to generate PCA in the absence of free LPS. Furthermore, direct exposure of highly purified monocytes to LPS did not induce PCA. LPS-triggered lymphocytes retained the capacity to induce monocytes for 4 hr after LPS exposure, after which they returned to an unstimulated state. LPS-triggered T-enriched lymphocytes required exposure to monocytes for as little as 15 min to fully induce monocytes to generate PCA during the following 4 to 6 hr. Continued exposure did not further amplify the response, although triggered lymphocytes could repeatedly collaborate with new monocytes to fully induce PCA. The stimulation of the lymphocyte and its capacity to trigger monocytes was not attenuated by inhibitors of protein or of RNA synthesis, whereas the capacity of the monocyte to generate PCA was abrogated by incubation with actinomycin D or cycloheximide, indicative of dependence on new RNA and protein synthesis. These observations delineate a rapid unidirectional pathway of lymphocyte-instructed monocyte function that should be considered as a potential participant in the initiation of the coagulation pathways in immunologic lesions and further illustrate the linkage between these basic host defense mechanisms.