Human skin mast cells: in vitro and in vivo studies.

OBJECTIVE: This short review surveys our current knowledge on the development and heterogeneity of human mast cells, the distribution of mast cells within human skin and the properties of human skin mast cells both in vitro and in vivo. It also examines the effects of antihistamines in the wheal-and-flare response in the skin provoked by bradykinin. RESULTS: Mast cells derive from mononuclear precursor cells which undergo their final phase of their differentiation in the tissues. In normal skin, mast cells, which are primarily of the MC(TC) subtype, occur in the greatest density in the superficial dermal zone. Like all other mast cells, human skin mast cells bind IgE with high affinity to specific FcepsilonRI receptors, but unlike those from lung, tonsils, adenoids or intestine, they also express the C5a receptor (CD88) and activation sites for substance P, VIP, somatostatin, and compound 48/80. Both IgE-dependent stimulation by activating tyrosine kinases, and non-immunologic stimulation by activating G-proteins induce a characteristic compound exocytosis resulting in the liberation of the preformed mediators. Production of prostaglandin D2 and leukotriene C4, however, occurs only with IgE-dependent stimulation. In vivo, dermal microdialysis and scanning laser Doppler imaging have been used to assess the role of histamine in the wheal-and-flare response. These techniques were also used to show that low concentrations of intradermal bradykinin release negligible quantities of histamine. The results showed that although the resultant flare was inhibitable by antihistamines, low concentrations of bradykinin released negligible quantities of histamine. This suggests a potentially novel mechanism of action of antihistamines that requires further detailed investigation.