Regulation of haemopoietic stem-cell proliferation in mice carrying the Slj allele.
We investigated a haemopoietic stromal defect, in mice heterozygous for the Slj allele, during haemopoietic stress induced by treatment with bacterial lipopolysaccharides (LPS) or lethal total body irradiation (TBI) and bone-marrow cell (BMC) reconstitution. Both treatments resulted in a comparable haemopoietic stem cell (CFU-s) proliferation in Slj/+ and +/+ haemopoietic organs. There was no difference in committed haemopoietic progenitor cell (BFU-e and CFU-G/M) kinetics after TBI and +/+ bone-marrow transplantation in Slj/+ and +/+ mice. The Slj/+ mice were deficient in their ability to support macroscopic spleen colony formation (65% of +/+ controls) as measured at 7 and 10 days after BMC transplantation. However, the Slj/+ spleen colonies contained the same number of BFU-E and CFU-G/M as colonies from +/+ spleens, while their CFU-s content was increased. On day 10 post-transplantation, the macroscopic 'missing' colonies could be detected at the microscopic level. These small colonies contained far fewer CFU-s than the macroscopic detectable colonies. Analysis of CFU-s proliferation-inducing activities in control and post-LPS sera revealed that Slj/+ mice are normal in their ability to produce and to respond to humoral stem-cell regulators. We postulate that Slj/+ mice have a normal number of splenic stromal 'niches' for colony formation. However, 35% of these niches is defective in its proliferative support.
D000483:Alleles; D000818:Animals; D001853:Bone Marrow / Q000528:radiation effects; D001854:Bone Marrow Cells; D016026:Bone Marrow Transplantation; D002455:Cell Division; D005260:Female; D006133:Growth Substances / Q000378:metabolism; D006410:Hematopoiesis; D016298:Hematopoietic Cell Growth Factors; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D012485:Salmonella typhi; D013154:Spleen / Q000166:cytology / Q000528:radiation effects; D014916:Whole-Body Irradiation
D006133:Growth Substances; D016298:Hematopoietic Cell Growth Factors; D008070:Lipopolysaccharides