Radioprotective effect of E. coli endotoxin on hematopoietic stem cells is partially suppressed by inhibiting production of nitric oxide by administering N-omega-nitro-L-arginine

Lipopolysaccharide of E. coli (LPS) injected to mice one day before the total gamma-irradiation caused a substantial increase in the level of endogeneous colonies formed in the spleen. It is known that this type of endotoxin may result in considerable production of nitric oxide from macrophages in different tissues. Therefore it is possible that the activation of hemopoietic stem cells after LPS-treatment was completely or partially stimulated by nitric oxide, which is the most important physiological mediator, or by action some other mediators (cytokines and growth factors) produced by hemopoietic microenvironment elements in response to the action of nitric oxide. This assumption was checked in experience with combined treatment of mice by LPS and a nonspecific inhibitor of nitric oxide production--N omega-nitro-1-arginine (NA). NA used in high dose (250 mg/kg) reduced partially (approximately by 30%) the LPS-increased level of spleen endogeneous colonies. When LPS was injected to mice 15 minutes after gamma-irradiation, this led to a slight increase in level of spleen colonies. In case when LPS was used together with NA after gamma-irradiation, this increase was still found.