Defective support of S1/S1d splenic stroma for humoral regulation of stem cell proliferation.
Humoral regulation of CFUs proliferation was investigated in S1/S1d mice characterized by a stromal defect, which severely limits in situ proliferation of in vivo colony-forming cells (CFUs). Injection of LPS-W evoked a large enhancement of CFUs numbers in the spleen of normal +/+ mice. S1/S1d mice were found to be refractory to low doses of LPS-W (up to 15 micrograms/mouse) and to have a diminished response to high doses (up to 150 micrograms). Serum transfer experiments showed that S1/S1d mice are not defective in the early elaboration (6 h) of a humoral factor (SHSF), which mediates the LPS-induced splenic stem-cell accumulation. In a serum-free in vitro system post-LPS S1/S1d and +/+ sera induced a similar degree of CFUs proliferation, indicating the ability of S1/S1d mice to produce normal levels of stem-cell-activating factor (SAF). Transfer of potent post-LPS serum from normal mice evoked a poorer splenic CFUs accumulation in S1/S1d mice as compared to normal +/+ littermates. The population size of splenic stem cells in S1/S1d mice parabiosed with normal +/+ mice also showed a limited increase in response to LPS-W injection. This diminished in vivo response of S1/S1d mice was not due to a decreased sensitivity of their CFUs for SAF, since S1/S1d and +/+ CFUs showed similar survival rates in vitro in the presence of SAF. We propose that the defective response of S1/S1d mice to LPS-induced humoral regulators is due to a nonmigratory component of the S1/S1d splenic stroma, which limits splenic CFUs proliferation either by a short-range inhibitory activity or by a deficiency of a local stimulatory activity or nutrient unlike SAF or SHSF, which might act in synergy with SAF.
D000748:Anemia, Macrocytic / Q000503:physiopathology*; D000818:Animals; D002453:Cell Cycle; D003114:Colony-Forming Units Assay; D006098:Granulocytes / Q000166:cytology; D006410:Hematopoiesis / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008817:Mice, Mutant Strains / Q000502:physiology*; D009000:Monocytes / Q000166:cytology; D010227:Parabiosis; D013154:Spleen / Q000473:pathology* / Q000503:physiopathology
D008070:Lipopolysaccharides