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We describe the potent effect of myriadenolide (Myr), a naturally occurring labdane diterpene, in promoting the production of eosinophils in cultured bone-marrow from several inbred mouse strains. This enhancing effect is lineage-selective and requires the eosinophil growth factors, Interleukin(IL)-5 or GM-CSF. Myr acts over a very low concentration range (10-10 M), if added at the beginning of the cell cultivation. Its enhancing effect increases between 24 h and 10 days of culture. We used both pharmacological and genetical tools to analyze its mechanism of action. Several lines of evidence show that the enhancing effect of Myr requires functional integrity of the 5-lipoxygenase (5-LO) pathway, and of CysLT receptors, which transduce the effects of cysteinyl-leukotrienes generated through this pathway. Myr also protects developing eosinophils from apoptosis induced by exogenous prostaglandin E2 (PGE), but not by NO, indicating that it acts upstream of NO in the PGE-initiated proapoptotic pathway which requires iNOS and CD95. Exposure to NO concentrations insufficient to induce apoptosis abolished the ability of eosinophils to respond to Myr, suggesting the involvement of a NO-sensitive cellular target. Myr has potential as a chemically defined research tool, which can be used to generate large numbers of eosinophils, thereby overcoming current limitations in the biochemical and molecular biological study of murine eosinophils, which has so far depended on complex, labor-intensive and long-term culture protocols for in vitro expansion.
Potent enhancing effects of Myr on eosinophil production in bone marrow stimulated by GM-CSF and IL-5 are mediated by the 5-LO pathway.
This article was published in the following journal.
Name: International immunopharmacology
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Neoplasms located in the bone marrow. They are differentiated from neoplasms composed of bone marrow cells, such as MULTIPLE MYELOMA. Most bone marrow neoplasms are metastatic.
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The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells.
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