Mechanisms towards compensation of long-term haemopoietic injury in mice after 5 Gy irradiation: In vivo and in vitro enhancement of superoxide anion production by granulocytes

Abstract

This paper analyzes the long-term (6 and 12 months) function of mouse granulocytes after total body irradiation with a single dose (5 Gy) of X-rays. Superoxide anion production has been investigated in granulocytes from peripheral blood, and also in those harvested from long term bone marrow cultures, with the aim of correlating the environmental damage induced by radiation with the functional properties of granulocytes. An in vivo and in vitro enhancement of superoxide anion production and protein levels in granulocytes from irradiated mice is described. The presence of some colony stimulating factor in the supernatant of cultures from irradiated mice could play an important role in the priming of granulocytes.

Glucose metabolism in bone marrow cells and granulocytes of adult mice after X‐ray (5 Gy) irradiation: relationship to cell functionality

“…As we have previously described (Gaitán et al, 1992), after 5 Gy irradiation, granulocytes enhance their capacity to produce superoxide anion. This oxyradical is generated in granulocytes by a NADPH-oxidase, therefore analysis of the enzyme substrate (NADPH) and the producing pathway may also render information about any functional damage in these cells after irradiation.…”

“…The enhanced protein synthesis observed (see Results) in the bone marow cells of irradiated mice could be due the expression of a higher proliferative activity of the reduced number of haemopoietic precursor cells to maintain blood cell number near their control levels (Gaitán et al, 1992). Protein synthesis accounts for 18-20% of the use of ATP in mammals (reviewed by Brown, 1992), so this increase in protein synthesis could be related to the reduction in ATP levels observed (Fig 3).…”

“…In spite of the apparently normal mature granulocytes we demonstrated that an increase in functional activity, such as the production of superoxide anion, takes place. This change was accompanied by the release of CSFs by stromal cells in the marrow (Gaitán et al, 1992Grande et al, 1993). Here, we analysed the possible metabolic and functional implications of irradiation in granulocytes and bone marrow cells (a heterogenous population with 60% of myeloid lineage) from mice irradiated with 5 Gy X-rays.…”

“…Peripheral blood granulocytes were isolated as previously described (Gaitán et al, 1992). Briefly, after red cell sedimentation in 0·1% methylcellulose (Dow Chemicals) for 30 min, the leucocytes were centrifuged onto Ficoll-Paque (Pharmacia) at 600 g for 20 min at 20ЊC.…”

“…However, our previous studies with external radiation and internal contamination with alpha particles ( 239 Pu) (Gaitán et al, 1992Grande et al, 1993), have demonstrated that, in spite of the restoration of normal haemopoiesis, a residual injury remains in the form of an enhanced capacity of mature granulocytes to produce superoxide anion. This increase could be due to the release of colony-stimulating factor (CSF) as a result of the irradiation.…”