Selective inhibition of the proliferation of various murine hemopoietic progenitor cells by cholera toxin.
We have studied in detail the effects of cholera toxin (CT), its pentameric B-chain subunit (toxoid) and the A-promoter chain on the differentiation of hemopoietic progenitor cells. Murine marrow cells were treated either with CT or its subunits. After stimulation with either the multilineage growth factor (multi-CSF; also called interleukin 3 or HCGF) or other hemopoietic regulators (colony-stimulating factors, or CSF), the clones grown in semisolid collagen cultures were scored in situ. Pluripotent stem cells (CFU-S) and multilineage (mixed CFU) or lineage-restricted progenitors (CFU-c) were estimated. We found that CT sensitivity is gradually gained by cells through the stepwise differentiation processes (i.e., CFU-S less than multilineage CFC less than committed CFC less than maturing cells). CT also has a selective, dose-dependent inhibitory effect (1 microM to 1 pM) on hemopoietic lineages (basophil-mast cells less than megakaryocytes less than neutrophils less than monomacrophages). These phenomena were obvious when the clonal growth was supported by multi-CSF but, interestingly, were not observed when lineage-restricted CSF were used. They furnished additional evidence that multi-CSF activates cells in a specific manner. This growth factor involved in progenitor cell self-renewal control may contribute to maintaining, on maturing cells, characteristics that are normally the attributes of progenitors.
D000818:Animals; D001491:Basophils / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D002772:Cholera Toxin / Q000494:pharmacology*; D003114:Colony-Forming Units Assay; D003115:Colony-Stimulating Factors / Q000037:antagonists & inhibitors; D006098:Granulocytes / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D007377:Interleukin-3; D008222:Lymphokines / Q000037:antagonists & inhibitors; D008407:Mast Cells / Q000187:drug effects; D008533:Megakaryocytes / Q000187:drug effects; D051379:Mice; D009000:Monocytes / Q000187:drug effects
D003115:Colony-Stimulating Factors; D007377:Interleukin-3; D008222:Lymphokines; D002772:Cholera Toxin