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

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 Ca2+, released LTB4 and histamine in response to SP. PD098059 significantly inhibited the release of LTB4, but not histamine in all strains. SB203580 failed to reduce or slightly impaired the release of LTB4. These results suggest that mast cells undergo maturation under the influence of fibroblasts, acquiring the responsiveness to SP with Ca2+ signals and predominantly ERK-MAP kinase.