Involvement of nitric oxide in the regulation of peripheral blood leukocyte counts

Abstract

A role for nitric oxide (NO) in the regulation of blood leukocyte numbers was examined in BALB/c mice by employing the NO synthase inhibitor NG-nitro L-arginine methyl ester (L-NAME). Treatment of animals with a single dose of 50 mg/kg body wt caused a dramatic increase in the number of circulating neutrophils and a moderate decrease in the number of circulating lymphocytes. These effects were partially reversed by the simultaneous inoculation of L-arginine (250 mg/kg body wt.) but not by D-arginine. A second NO synthase inhibitor, NG-nitro L-arginine, induced changes comparable to those elicited by L-NAME. Because catecholamines and glucocorticoids are well-known modulators of blood leukocyte counts, experiments were carried out in adrenalectomized mice. It was found that adrenalectomy did not modify the increase in the number of circulating neutrophils induced by L-NAME but completely prevented the decrease of circulating lymphocytes. Taken together, these findings support the hypothesis that NO plays an important role in the regulation of the peripheral blood number of neutrophils and lymphocytes, and that this function involves, in each case, the participation of different mechanisms.

Antioxidants restore protoporphyrinogen oxidase in variegate porphyria patients

“…However, recent meta-analysis re-examining the relationship between supplemental vitamin E and all-cause mortality concluded that supplementation with vitamin E appears to have no effect on all-cause mortality at doses lower than 400 IU/day, which are higher than the doses used in our study [33,34]. The mechanisms by which the supplementation with antioxidant vitamins induces lymphopenia are not clear, although an increase in the levels of corticosteroids in response to ascorbate could be involved [39,40]. Studies using amounts of vitamin C about 500 mg/day reported possible prooxidant effects, whereas at lower levels were only reported antioxidant effects [35,36].…”

“…In previous experiments, we also detected a decrease in the number of circulating lymphocytes after vitamins C and E supplementation [37,38]. The mechanisms by which the supplementation with antioxidant vitamins induces lymphopenia are not clear, although an increase in the levels of corticosteroids in response to ascorbate could be involved [39,40].…”

Biphasic role for nitric oxide in experimental renal warm ischaemia–reperfusion injury

“…Nitric oxide helps to maintain renal blood¯ow and prevent postischaemic vasospasm 44 and microvascular dysfunction 45 with a concomitant reduction in endothelium± neutrophil interaction which should limit postischaemic renal failure 46 . Nitric oxide also inhibits neutrophil chemotaxis, production of oxygen and enzyme release 47 .…”

Chronic blockade of nitric oxide biosynthesis in rats: effect on leukocyte endothelial interaction and on leukocyte recruitment

“…L-NAME treated mice presented lymphopenia and neutrophilia, which were partially reversed by L-Arg administration [28]. These effects may interfere with leukocyte/endothelial interactions, since up and down modulation of adhesion molecules are observed during the intermediate stages of leukocyte maturation [29].…”