Effects of endotoxin on hematopoiesis in irradiated and nonirradiated W/W(v) mice

Abstract

The interaction between the genetically deficient hematopoietic stem cells of W/W(v) mice and the stimulation produced by bacterial endotoxin in irradiated and nonirradiated mice was studied. Effects of 25 μg S. typhosa endotoxin injected 1 day before irradiation proved to be similar to effects in +/+ normal mice in several respects. After 300 rads survival was increased from 23% to 77%, recovery of hemoglobin concentration began on day 13 rather than day 17 and granulocyte concentrations were maintained at approximately 1500 per mm3 compared to a drop to 350 per mm3 on day 17 in those given no endotoxin. Erythrocytic spleen colonies were negligible whether or not endotoxin was given. Endotoxin induced granulocytic colonies in significant numbers as early as 5 days after 300 rads, but their peak number (on day 7) was comparable to that seen 4 days after 700 rads in endotoxin treated +/+ mice. Spleen and femur cells of nonirradiated W/W(v) mice given 9 daily endotoxin injections produced very few erythrocytic colonies on transplantation into normal irradiated recipients, but a fairly substantial number of granulocytic colonies. This number was, nevertheless, far below that for spleen or femur cells of +/+ mice. When W/W(v) mice were used as recipients instead of irradiated +/+ mice cells from both normal and W/W(v) failed to produce granulocytic colonies. It is concluded that endotoxin acts as a stem cell and granulopoietic stimulus in W/W(v) mice as it does in +/+ mice, the cellular response to this stimulus being sluggish and subnormal as it is with other stimuli in W/W(v) mice.