Human skin mast cells: in vitro and in vivo studies

Objective: This short review surveys our current knowledge on the developme nt and heterogeneity of human mast cells, the distribution of mast cells wi thin human skin and the properties of human skin mast cells both in vitro a nd 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 t heir final phase of their differentiation in the tissues. In normal skin, m ast cells, which are primarily of the MC, subtype, occur in the greatest de nsity in the superficial dermal zone. Like all other mast cells, human skin mast cells bind IgE with high affinity to specific Fc epsilon RI receptors , but unlike those from lung, tonsils, adenoids or intestine, they also exp ress the C5a receptor (CD88) and activation sites for substance P, VIP, som atostatin, 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 D-2 and leukotriene C -4, however, occurs only with IgE-dependent stimulation. In vivo, dermal mi crodialysis and scanning laser Doppler imaging have been used to assess the role of histamine in the wheal-and-flare response. These techniques were a lso used to show that low concentrations of intradermal bradykinin release negligible quantities of histamine. The results showed that although the re sultant flare was inhibitable by antihistamines, low concentrations of brad ykinin released negligible quantities of histamine. This suggests a potenti ally novel mechanism of action of antihistamines that requires further deta iled investigation.