The release of leukotriene B sub(4) from human skin in response to substance P: evidence for the functional heterogeneity of human skin mast cells among individuals

Substance P is located in cutaneous nerve fibres and induces wheal and flare responses, accompanied by granulocyte infiltration, upon intradermal injection. Studies with animal skin and rat peritoneal mast cells have suggested that substance P induces the release of histamine and leukotriene B sub(4) (LTB sub(4)), a potent chemoattractant for granulocytes, from skin mast cells. However, the release of LTB sub(4) has not been detected from mast cells enzymatically isolated from human skin. In order to investigate the mechanism of granulocyte infiltration induced by substance P in human skin, we studied the release of LTB sub(4) and histamine in response to substance P, and the effect of dexamethasone using human skin obtained from 22 nonallergic individuals. Histamine was released from all skin tissue samples in a dose-dependent manner. However, the amount of LTB sub(4) release, both constitutive and inducible, was variable among skin preparations. Substance P induced a large release of LTB sub(4) from the skin of eight donors (twice to six times that of the spontaneous release), but no or only negligible release from the skin of 14 donors. The amount of constitutive release of LTB sub(4) correlated with the amount of tissue histamine. Dexamethasone selectively abolished the inducible release of LTB sub(4), without an effect on histamine release and the constitutive release of LTB sub(4). These results suggest that substance P induces the release of LTB sub(4) in a certain population of human individuals by a glucocorticosteroid-dependent mechanism, and plays an important role in neurogenic inflammation with granulocyte infiltration.