A relationship between residual stromal damage in hematopoietic tissue and the functional activity of granulocytes

This paper analyzes the function of mouse granulocytes in the long term, after external irradiation with x- and gamma-rays and 239Pu contamination at different gestational ages and in a variety of culture conditions. These treatments can produce persistent defects in the stroma, which regulates hematopoiesis. Superoxide-anion production has been measured in granulocytes from peripheral blood and from long-term bone marrow cultures (LTBMC). A significant enhancement of O2- is produced using single or fractionated doses of x-rays; however, little or no increase is observed with gamma-rays. With 239Pu, enhancement of O2- depends on gestational age at contamination. The absence of hydrocortisone (HC) in LTBMC and the irradiation of the adherent layer with 15 Gy stimulate O2- production. The increased production of O2- appears to be correlated with an excess of colony-stimulating factors (CSFs) released to the supernatant by stromal cells. Neutralization with anti-granulocyte-macrophage CSF (anti-GM-CSF) monoclonal antibody shows that GM-CSF is the main factor produced. In summary, conditions that lead to residual stromal damage also result in the generation of granulocytes that are functionally primed for excess superoxide-anion production.