calcimycin and Multiple-Sclerosis

Topics: Blood Platelets; Calcimycin; Cell Communication; Granulocytes; Humans; Multiple Sclerosis; Neutrophils

The calcium ionophore A23187-induced adherence inhibition of mononuclear leucocytes and granulocytes in multiple sclerosis patients and in controls was investigated. Furthermore, the role of thrombocytes in the ionophore-induced adherence inhibition of both the mononuclears and the granulocytes was evaluated. In the control group and in patients treated with corticosteroids the ionophore consistently induced the adherence inhibition of mononuclear leucocytes. In multiple sclerosis patients without corticosteroid treatment rather heterogenous results were obtained, which appears to reflect the fluctuation of the disease activity. Addition of thrombocytes to the mononuclear leucocyte suspension led to a decrease of leucocyte adherence in both multiple sclerosis groups regardless of the presence of the ionophore. The ionophore stimulation of granulocytes preincubated with the thrombocyte suspension resulted in an increase of the granulocyte nonadherence in healthy controls. An analogous response in multiple sclerosis patients without corticosteroid treatment was significantly less expressed and was not found in patients treated with corticosteroids. These results suggest a thrombocyte-dependent alteration of the membrane properties in the early phase of nonspecific granulocyte activation in patients with multiple sclerosis.

Topics: Adrenal Cortex Hormones; Analysis of Variance; Blood Platelets; Calcimycin; Cell Adhesion; Granulocytes; Humans; Leukocyte Adherence Inhibition Test; Leukocytes, Mononuclear; Multiple Sclerosis

In patients with disseminated sclerosis and in a control group inhibition of granulocyte adherence was investigated after stimulation with the ionophore A23187 and the effect of autologous thrombocytes on this reactivity was investigated. The granulocyte adherence was not markedly influenced in the described experimental set-up by the ionophore alone not by incubation with thrombocytes alone. The ionophoretic stimulation of granulocytes incubated with thrombocytes caused marked inhibition of leucocyte adherence in healthy controls and to a significantly smaller extent in patients with multiple sclerosis without corticosteroid treatment. In patients treated with corticosteroids this response was not observed. The results suggest a change of membrane properties, dependent on thrombocytes, in the early stage of non-specific granulocyte activation in patients with multiple sclerosis.

Topics: Blood Platelets; Calcimycin; Cell Adhesion; Granulocytes; Humans; Multiple Sclerosis

The author assessed the effect of leucotrienes B4 and C4 and the calcium ionophore A23187 on the adherent reactivity of mononuclear leucocytes in patients with multiple cerebrospinal sclerosis and in controls. The calcium ionophore A23187 in concentrations of 200 nmol/1 - 5 mumol/1 induced inhibition of leucocyte adherence, depending on the concentration used. This reactivity was, as compared with controls, significantly lower in patients with multiple sclerosis who did not take cortisoid preparations and in patients taking prednisone in doses up to 5 mg/day. In patients treated with higher prednisone doses (20-90 mg/day) the values of the non-adherence index reached values insignificantly higher than in controls. Leukotrienes B4 and C4 (1 nmol/1 - 100 nmol/1 stimulated leucocyte adherence in patients treated with higher corticoid doses, in the remaining patients and in controls they did not influence the leukocyte adherence. The results of the investigation provide evidence of abnormalities of the membrane properties of the mononuclear leucocytes in patients with multiple sclerosis and draw attention to the association of these changes with metabolic chains of arachidonic acid and with calcium ion homeostasis.

Topics: Adult; Calcimycin; Female; Humans; Immunologic Techniques; Leukocyte Adherence Inhibition Test; Leukotriene B4; Male; Middle Aged; Multiple Sclerosis; SRS-A

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.

Topics: Adult; Calcimycin; Calcium; Female; Humans; Leukocyte Adherence Inhibition Test; Leukocytes, Mononuclear; Leukotriene B4; Male; Middle Aged; Multiple Sclerosis; SRS-A

Release of leukotriene B4 (LTB4) and leukotriene C4 (LTC4) from neutrophils and platelet-neutrophil suspensions in response to ionophore A23187 was measured in 12 multiple sclerosis (MS) patients and 8 healthy volunteers. LTC4 release from neutrophils, as well as from platelet-neutrophil suspensions, was significantly decreased in MS patients compared with the controls. There was no significant difference in the release of LTB4 between MS patients and controls. The findings suggest that permanent stimulation of platelets and neutrophils e.g., by encephalitogenic peptide leads to continuous LTC4 release with subsequent depletion of intracellular substrates serving as precursors for the formation of 5-lipoxygenase products. Since the target of microvascular actions of LTC4 are postcapillary venules, the release of this sulfidopeptide leukotriene might play a pathogenetic role in the formation of MS lesions.

Topics: Adult; Blood Platelets; Calcimycin; Female; Humans; Leukotriene B4; Male; Middle Aged; Multiple Sclerosis; Neutrophils; SRS-A