Bone marrow derived mast cell acquire responsiveness to substance P with Ca2+ signals and release of leukotriene B4 via mitogen-activated protein kinase

Abstract Substance P (SP) selectively activates mast cells that reside in connective tissues. We studied the reactions of bone marrow-derived mast cells (BMMC) of three mouse strains, cultured with or without fibroblasts. BMMC co-cultured with fibroblasts, but not those cultured alone, increased intracellular Ca 2+ , released LTB 4 and histamine in response to SP. PD098059 significantly inhibited the release of LTB 4 , but not histamine in all strains. SB203580 failed to reduce or slightly impaired the release of LTB 4 . These results suggest that mast cells undergo maturation under the influence of fibroblasts, acquiring the responsiveness to SP with Ca 2+ signals and predominantly ERK-MAP kinase.