Bone marrow-derived mast cells in mice respond in co-culture to scorpion venom activation of superior cervical ganglion neurites according to level of expression of NK-1 receptors

In virtually all tissues of the body, mast cells are closely associated with nerve fibers, mostly of sensory origin. While mast cells can be activated by substance P, evidence for the involvement of NK-1 receptors is very limited. To study functional interactions between mast cells and peripheral nerves, bone marrow-derived mast cells (BMMC) and superior cervical ganglia (SCG) were co-cultured. Murine bone marrow-derived mast cells are homologues for mucosal mast cells and have recently been shown to express NK-1 receptors. Bi-directional interaction was studied using a fluorescent calcium indicator as an index of cellular activation. Scorpion venom, not affecting BMMC by itself, caused a rapid increase in neurite fluorescence subsequently followed by activation of the mast cell. The latter was inhibited by the NK-1 receptor antagonist SR140333, showing the direct involvement of substance P and its receptor in this co-culture system. Activation of BMMC seemed to be directly correlated with extent of NK-1 receptor expression. Immature c-kit positive cells not expressing NK-1 gave a negligible response to neurite activation. In addition, there was a maximum stimulation occurring when NK-1 expression exceeded 16% on BMMC after cytokine stimulation. Our findings show that the expression of NK-1 receptors appears to be important for nerve-mast cell communication.