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Sphingosine-1-phosphate induces development of functionally mature chymase-expressing human mast cells from hematopoietic progenitors

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Mast cells (MCs) play a critical role in both acute and chronic inflammation and mature in peripheral tissues from bone marrow-derived progenitors that circulate in the blood as immature precursors. MCs developed from cord blood-derived progenitors cultured with stem cell factor (SCF) alone express intragranular tryptase (MC T s), the phenotype predominant in the lung. MC progenitors are likely to encounter the serum-borne bioactive sphingolipid metabolite, sphingosine-1-phosphate (S1P), during migration to target tissues. S1P accelerated the development of cord blood-derived MCs (CB-MCs) and strikingly increased the numbers of MC-expressing chymase. These MCs have functional Fc RIs, and similar to skin MC TC s that express both tryptase and chymase, also express CD88 and are activated by anaphylatoxin C5a and the secretagogue compound 48/80. S1P induced release of IL-6, a cytokine known to promote development of functionally mature MC TC s, from cord blood cultures containing adherent macrophages, and from highly purified macrophages, but not from macrophage-depleted CB-MCs. In contrast, S1P stimulated secretion of the chemokine, monocyte chemoattractant protein 1 (MCP-1/CCL2), from these macrophage-depleted and purified CB-MCs. These results suggest crucial roles for S1P in regulating development of human MCs and their functions and reveal a complex interplay between macrophages and MC progenitors in the development of mature human MCs.—Price, M. M., Kapitonov, D., Allegood, J., Milstien, S., Oskeritzian, C. A., Spiegel, S. Sphingosine-1-phosphate induces development of functionally mature chymase-expressing human mast cells from hematopoietic progenitors.

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Article Details
Price, Megan M.; Kapitonov, Dmitri; Allegood, Jeremy; Milstien, Sheldon; Oskeritzian, Carole A.; Spiegel, Sarah
The FASEB Journal , Volume 23 (10): 3506
Fed of American Socs for Experimental BiologyOct 1, 2009
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