Studies on the Regulation of Diffusion Chamber Granulopoiesis
We have evaluated the role of colony-stimulating activity (CSA) and stem cells in diffusion chamber (DC) myelopoiesis. CF1 host mice were implanted with DC with 0.5 x 106 normal marrow cells and then injected for 3–4 days intravenously with 5 μg Salmonella typhosa endotoxin or saline. There were no significant increases in DC myelopoiesis, but significant increases in host animal total tibial proliferative granulocytes on day 4 and suggestive increases in nonproliferative granulocytes on day 7 of DC culture. Further studies utilizing progressively increasing doses of intravenous endotoxin in irradiated or normal host mice implanted with DC with normal marrow showed: (1) a lack of correlation of serum CSA or inhibitor level with DC myelopoiesis; (2) elevations of CSA levels within DC relative to serum levels in all groups; and (3) a general inverse correlation of DC myelopoiesis with marrow cellularity.
Further studies evaluated the DC growth of murine marrow depleted of CFU-S by in vitro exposure to absorbed mouse brain antiserum plus complement. There was little effect of this treatment on DC-differentiated or stem cell recovery. These results raise questions with regard to the nature of the DC stem cell and the actual effect of mouse brain antisera on murine hemopoietic stem cells.
In toto, the above suggests that DC cell growth may, in part, be regulated by a negative feedback based on marrow cellularity. The identity of the DC stem cell and the role of CSA in regulating DC myelopoiesis remain open questions.
KeywordsMarrow Cell Fetal Liver Diffusion Chamber Culture Normal Seron Host Mouse
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