FcγRIIa, not FcγRIIb, is constitutively and functionally expressed on skin-derived human mast cells

The expression of FcyR by human skin-derived mast cells of the MCTC type was determined in the current study. Expression of mRNA was analyzed with microarray gene chips and RT-PCR; protein by Western blotting and flow cytometry; function by release of beta-hexosaminidase, PGD(2), leukotriene C-4 (LTC4), IL-5, IL-6, IL-13, GM-CSF, and TNF-alpha. Fc gamma RIIa was consistently detected along with Fc epsilon RI at the mRNA and protein levels; Fc gamma RIIc was sometimes detected only by RT-PCR; but Fc gamma RIIb, Fc gamma RI, and Fc gamma RIII mRNA and protein were not detected. Fc gamma RIIa-specific mAb caused skin MCTC cells to degranulate and secrete PGD(2), LTC4, GM-CSF, IL-5, IL-6, IL-13, and TNF-alpha in a dose-dependent fashion. Fc epsilon RI-specific mAb caused similar amounts of each mediator to be released with the exception of LTC4, which was not released by this agonist. Simultaneous but independent cross-linking of Fc epsilon RI and Fc gamma RIIa did not substantially alter mediator release above or below levels observed with each agent alone. Skin MCTC cells sensitized with dust-mite-specific IgE and IgG, when coaggregated by Der p2, exhibited enhanced degranulation compared with sensitization with either IgE or IgG alone. These results extend the known capabilities of human skin mast cells to respond to IgG as well as IgE-mediated signals.