Effect of calcium ionophore A23187 and of leukotrienes B4 and C4 on the adherence of mononuclear leucocytes in multiple sclerosis.

The disturbances of the arachidonic acid metabolic cascade are supposed to play a significant part in some membrane alterations and in associated immunopathological changes in multiple sclerosis. Since the lipoxygenase derivatives of the arachidonic acid and the calcium ion influx were proved to participate in the mechanisms involved in the leucocyte adherence inhibition phenomenon, the effect of calcium ionophore A23187 and of leukotrienes B4 and C4 upon the adherence of mononuclear leucocytes of multiple sclerosis patients and of healthy controls was investigated in the present study using a modification of the leucocyte adherence inhibition assay. A23187, a potent stimulator of the arachidonic acid metabolism, induced the mononuclear leucocyte adherence inhibition in a dose-dependent manner. In multiple sclerosis patients without corticosteroid treatment and in those treated with lower prednison doses (up to 5 mg/day), the non-adherent response to A23187 stimulation was significantly lower than in the controls, whereas in multiple sclerosis patients treated with prednison doses varying from 20 to 90 mg/day the A23187-induced adherence inhibition reached non-significantly higher values compared to the controls. Leukotrienes B4 and C4 stimulated the adherence of the leucocytes in multiple sclerosis patients treated with higher prednison doses. Compared to controls, statistically significant differences were found using 1 nM and 100 nM LTC4. The findings obtained in this study with all probability reflect alterations of the membrane processes in multiple sclerosis leucocytes associated with calcium ion homeostasis and arachidonic acid metabolic cascade.