Prostaglandin E(2) and stem cell factor can deliver opposing signals to B lymphocyte precursors.
The synthetic prostanoid, 16,16-dimethyl PGE(2), suppressed B lymphopoiesis in mice and proliferation of normal B cell precursors or the F10 pro-B cell line to interleukin 7 in culture. This was not the case with two other prostanoids, PGD(2) and PGF(2alpha), or agonists for PGI(2) agonist and thromboxane A(2) agonist receptors. PGE(2), but not the related prostanoids or agonists, induced apoptosis in F10 cells. The apoptotic response was mediated by the EP2 class of PGE(2) receptors and required an increase in intracellular cyclic adenosine 3',5'-monophosphate, activation of protein kinase A, and protein synthesis. The influence of PGE(2) on F10 cells was diminished in the presence of a cloned stromal cell line or stem cell factor. These findings describe another potential regulatory circuit in bone marrow which might influence B lymphopoiesis under disease or steady-state conditions.
Shimozato
T
T
Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 73104, USA.
Kincade
P W
PW
D000818:Animals; D017209:Apoptosis / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology* / Q000378:metabolism; D001854:Bone Marrow Cells / Q000276:immunology; D002450:Cell Communication / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D002460:Cell Line; D002999:Clone Cells / Q000276:immunology; D000242:Cyclic AMP / Q000378:metabolism; D015232:Dinoprostone / Q000502:physiology*; D006410:Hematopoiesis / Q000276:immunology; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D018078:Receptors, Prostaglandin E / Q000502:physiology; D058307:Receptors, Prostaglandin E, EP2 Subtype; D015398:Signal Transduction / Q000276:immunology*; D019089:Stem Cell Factor / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D017154:Stromal Cells / Q000276:immunology; D015854:Up-Regulation / Q000276:immunology
D007166:Immunosuppressive Agents; C545645:Ptger2 protein, mouse; D018078:Receptors, Prostaglandin E; D058307:Receptors, Prostaglandin E, EP2 Subtype; D019089:Stem Cell Factor; D000242:Cyclic AMP; D015232:Dinoprostone