Lymphokines and thrombosis. Effect of lymphokines on fibrinolysis. Release of fibrinolytic activity by human leucocytes stimulated with lymphokines.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to E Coeugniet.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Human lymphokines can elicit several effects associated with inflammation, e.g. leucocyte migration inhibition and fibrinolysis. These effects can be assessed in vitro by the leucocyte migration agarose technique (LMAT) and the leucocyte migration fibrinolysis technique (LMFT). The present study shows that preincubation of normal leucocytes with aprotinin, tranexamic acid and phenyl-methyl-sulfonylfluoride (PMSF) reduces or abolishes their migration inhibition response to leucocyte migration inhibition factor. The compounds exert this effect at non-toxic concentrations, which do not otherwise interfere with migration or fibrinolysis, and are non-toxic as estimated by PHA stimulation of lymphocytes. The LMFT is more sensitive to the modifying effect than the LMAT. The effect of aprotinin and tranexamic acid is reversible, the effect of PMSF is irreversible.
Lymphocytes from 14 patients treated with a combination of acetylsalicylic acid (ASA) and dipyridamole (DIPY) showed a decreased ability to produce leucocyte migration inhibitory activity (LMIA) when stimulated with concanavalin-A (ConA). The combined treatment also produced a decrease of leucocyte response to a standard LMIA-containing culture supernatant. Treatment with only one of the two drugs did not cause detectable alteration of the lymphocyte response to Con-A or the leucocyte response to LMIA. In vitro, both DIPY and ASA were independently effective in decreasing the LMIA production of Con-A-stimulated lymphocytes and the leucocyte response to a standard LMIA-containing culture supernatant.
Human leucocytes can migrate in a gel medium consisting of fibrin, 10% horse serum and tissue culture medium 199. The cells migrate within the fibrin gel mass. The 24 h. areas of migration depend upon the volume and concentration of the cell suspension applied on the fibrin gel. The amount of cells per mm2 migration culture area is less than half the amount used in the leucocyte migration agarose test. The results are reproducible, the standard variation of the migration areas is below 10%. The method is potentially useful for several purposes such as for measuring fibrinolytic and migratory activity of granulocytes, monocytes and lymphocytes and modification of these functions by lymphokines.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
The in vitro effects of heparin, dipyridamole (DIPY) and lysine-acetylsalicylate (LASA) on human peripheral blood leucocyte migration and upon production/release and effect of leucocyte migration inhibitory activity (LMIA) from lymphocytes stimulated with concanavalin-A (con-A) have been studied. The final concentration of each drug was of the same order of magnitude as during clinical treatment. The leucocyte migration under agarose was significantly increased by DIPY at a concentration of 100 mug/ml. The release/production of LMIA was inhibited by DIPY at 1 mug/ml and by LASA at 0.3 mug/ml. Heparin had no influence on LMIA release, even at 10 IU/ml. The LMIA of supernatants from con-A-stimulated lymphocyte cultures was inhibited by DIPY at a concentration of 10 mug/ml, by LASA at 3 mug/ml and by heparin at 10 IU/ml. The findings suggest that DIPY and LASA could have a dual role as modifiers of inflammation: 1) the well known role as antiaggregants tending to limit and impede thrombosis, and 2) as antagonists to the lymphocyte-mediated (type IV) immune reaction through a depressive action on lymphokine production/release and activity.
Human lymphocytes stimulated with concanavalin-A produce a coagulant activity which decreases the clotting time as expressed through the recalcification time of citrated plasma, the partial thromboplastin time, the thrombin clotting time of citrated plasma and the thrombin clotting time of fibrinogen solutions. The culture supernatants of human lymphocytes stimulated with concanavalin-A also have a direct coagulant effect on human fibrinogen solution. They decrease the lag period of recalcification time of citrated plasma but do not modify the duration of polymerization as measured with a spectrophotometric method.
Leucocyte migration and migration inhibition in fibrin medium may reveal new aspects of lymphokine activity associated with immunological inflammation. Leucocyte migration fibrinolysis technique is compared with the leucocyte migration capillary technique and the leucocyte migration agarose technique. In the present model experiment the three methods gave comparable results. The leucocyte migration fibrinolysis technique involves a new principle for detection of lymphokines and can probably be developed to give more exact information about the interrelationship between thrombosis, fibrinolysis and lymphokines.
Supernatants from Con-A stimulated human lymphocytes containing leucocyte migration inhibitory activity were measured for thrombocyte aggregation activity and for influence on thrombocyte rich plasma clot retraction and whole blood clot retraction. The lymphocyte released activity of the supernatants produced thrombocyte aggregation and an acceleration of clot retraction. The activity resisted heating at 56 degrees C for 30 min and was inactivated at 80 degrees C for 30 min. The active substance seems to have a molecular weight above 10,000 daltons. The findings suggest that thrombotic processes associated with cell-mediated (type IV) immune inflammation could be due, at least partially, to lymphokine effects on thrombocytes.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.