Reactive oxygen and nitrogen species in the course of B-CLL.

PURPOSE

The study objective was to investigate the production of NO, cGMP and superoxide anion radical by neutrophils, and to examine alterations in serum or plasma total nitric oxide, MDA and cGMP levels in B-CLL patients.

MATERIAL AND METHODS

PMNs were isolated from 20 patients with B-CLL. Total nitrite was measured in cell supernatants and serum by Griess method. The generation of superoxide anion radical by cells was estimated using cytochrom-c reduction test. The cGMP level in cell supernatants and plasma was assessed by ELISA kit whereas serum MDA level using a spectrophotometric assay by Guege and Aus.

RESULTS

The PMNs in B-CLL patients were characterised by impaired NO generation and enhanced cGMP production. Contrary to the control group, no significant effect was found of rhlL-15 and rhIL-18 on the release of these mediators by PMNs. Superoxide anion radical release by PMNs was decrease. Serum MDA and plasma cGMP levels were elevated in B-CLL patients as compared to the controls.

CONCLUSIONS

The reduced production of nitric oxide and superoxide anion radicals by PMNs in B-CLL may impair the cytotoxic effect of neutrophils on leukaemic B cells. Low secretion of nitric oxide by PMNs and high levels of cGMP in PMN supernatants suggest that activation of guanyl cyclase (sGC) in these patients may occur in the presence of agents other than nitric oxide. Moreover, the findings indicate the enhancement of lipid peroxidation with the progression of the neoplastic process in B-CLL patients.