Effect of Endotoxin on the Kinetics of Hemopoietic Colony-Forming Cells in Irradiated Mice

Abstract

Hemopoietic recovery in irradiated animals is hastened by the action of bacterial endotoxin given as a single injection either before or shortly after irradiation (1). Bone marrow cellularity, peripheral blood granulocyte, erythrocyte, platelet, and lymphocyte concentrations, and survival are favorably affected and, in the mouse, the number of endogenous spleen colonies is increased (2-4). The fact that endotoxin is effective when given after irradiation rules out several modes of action. These include chemical protection, hypoxia, increased numbers of stem cells at the time of irradiation, and decreased sensitivity of the stem cells to the immediate killing action of radiation. Among the possibilities remaining are recovery of cells that otherwise would die on the resumption of mitosis, early resumption of mitosis, and shortening of the cell cycle. Means of exploring such possibilities are provided by the technique for enumerating colony-forming units (CFU) developed by Till and McCulloch (5-7). Suspensions containing hemopoietic cells are injected into recipient mice whose endogenous spleen colony formation has been suppressed by lethal irradiation and the resulting spleen colonies are counted 10 days later. The transplanted colonyforming units have many of the characteristics of stem cells (8), and in the present experiments we assume that their enumeration provides an assay of stem cells. The experiments presented here concern population changes in colony-forming units in spleen and femoral marrow resulting from an injection of Salmonella typhosa endotoxin 24 hours before or a few minutes after irradiation with 400 rads.