Differential elaboration of prostaglandin E2 by cells of the hemopoietic microenvironment in response to endotoxin.
Eight daily intraperitoneal injections of endotoxin (LPS) induced hematologic abnormalities in mice like those previously observed with chronic inflammation, sterile abscess, and tumor bearing. By the ninth day, anemia, leukocytosis, hypocellularity of the bone marrow, and compensatory hemopoietic hyperplasia of the spleen had occurred. The suppressed hemopoietic recovery and impaired survival of mice with these abnormalities, after receiving an ordinarily sublethal dose of total body irradiation (600 cGy T.B.), confirmed their importance to the intact mouse and suggested that splenic hyperplasia was insufficient to compensate for a total body deficit of functional hemopoietic stem cells. Atrophy of hemopoietic tissue in the marrow with hyperplasia in the spleen implicated changes in the hemopoietic microenvironment to account for the different responses to endotoxin. Prostaglandin E2 (PGE2) serves as an important mediator of the inflammatory response and profoundly affects hemopoiesis. Previous studies had shown that low concentrations of PGE2 enhanced, and high concentrations suppressed erythropoiesis in vitro; therefore, we wondered whether stromal cells from the marrow's microenvironment produced more PGE2 in response to LPS than splenic stromal cells to explain the suppression of hemopoiesis in the marrow and its enhancement in the spleen. Indeed, synthesis of PGE2 in primary short-term cultures of adherent marrow stromal cells in response to LPS proved much greater than that observed in cultures of splenic stromal cells. Extending adherence times from 3 to 24 to 48 hours did not change the relationship. We believe that the results of our studies point to a role of PGE2 in the microenvironmental modulation of hemopoiesis in mice with activation of the inflammatory response.
DeGowin
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D000818:Animals; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology; D002448:Cell Adhesion; D015232:Dinoprostone; D004731:Endotoxins / Q000633:toxicity*; D004920:Erythropoiesis / Q000187:drug effects / Q000528:radiation effects; D004926:Escherichia coli; D005260:Female; D006410:Hematopoiesis / Q000187:drug effects* / Q000528:radiation effects; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D007213:Indomethacin / Q000494:pharmacology; D051379:Mice; D011458:Prostaglandins E / Q000096:biosynthesis*; D013154:Spleen / Q000378:metabolism / Q000473:pathology; D014916:Whole-Body Irradiation
D004731:Endotoxins; D011458:Prostaglandins E; D015232:Dinoprostone; D007213:Indomethacin