Role of splenic stroma in the action of bacterial lipopolysaccharides on radiation mortality: a study in mice carrying the Sl j allele

. Sl j /+ mice display a slight macrocytic anaemia due to a defect in their haemopoietic organ stroma. They have a deficient endogenous spleen colony (CFU‐end) formation following sublethal doses of gamma‐radiation compared with their normal +/+ littermates, which is likely to be due to the low pre‐irradiation CFU‐S content of the Sl j /+ spleen. CFU‐S in these congenic mice do not differ in their sensitivity to gamma‐irradiation or stem cell‐activating factor. While injection of +/+ mice with 10 μ g of lipopolysaccharide‐W (LPS) one day prior to irradiation led to a substantial increase in their survival, the survival of Sl j /+ mice was only slightly increased. Irradiation induced a similar dose‐related reduction in the numbers of CFU‐S in the spleen and femora of LPS‐injected Sl j /+ mice compared to similarly treated +/+ mice when measured directly after irradiation. At Day 9 after irradiation, injection of LPS led to a significantly higher CFU‐end formation and higher numbers of CFU‐S and nucleated cells in the Sl j /+ spleens compared to LPS‐injected +/+ mice. No such differences in the radioprotective effect of LPS were observed in the +/+ and Sl j /+ mice with respect to the splenic and femoral 59 Fe‐incorporation and the femoral CFU‐S numbers at Day 9. These data strongly suggest a contribution by immigrating CFU‐S to the CFU‐S numbers and endogenous colony formation in at least the Sl j /+ spleen after LPS injection and subsequent sublethal irradiation. The observations also imply that the splenic organ stroma may play a mediatory role in the radioprotective action of LPS. In addition, the data represent an extreme example of a lack of correlation between animal survival and haemopoietic parameters. Caution should be taken when applying endogenous colony counts as a means of screening potential anti‐radiation drugs.