Bone marrow derived mast cell acquire responsiveness to substance P with Ca(2+) signals and release of leukotriene B(4) 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 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.