Histamine receptor H4 regulates mast cell degranulation and IgE induced FcεRI upregulation in murine bone marrow-derived mast cells

There is increasing evidence that histamine regulates the immune system via histamine H4 receptors, therefore we sought to investigate the functions of the H4 receptor on mast cells. Mast cells were differentiated from murine bone marrow stem cells, and the expression of mast cell surface markers Fc epsilon RI and CD117 were measured using flow cytometry. Real-time qRT-PCR was used to determine the expression of mH4R; as a measure of antigen-dependent degranulation, beta-hexosaminidase release assay was carried out using IgE sensitized mast cells. We determined that the expression kinetics of Fc epsilon RI and mH4R can be described with a function that has one maximum value in the time range of the culture's differentiation. Antigen-dependent degranulation of murine bone marrow-derived mast cells could be inhibited by a selective H4 antagonist/inverse agonist only when it was present during the IgE sensitization phase of degranulation. In addition, flow cytometric analysis revealed that the H4 antagonist/inverse agonist also inhibited IgE induced Fc epsilon RI upregulation. The inhibition percentage of H4 antagonist on IgE induced Fc epsilon RI upregulation was determined to be dependent upon the maturity of the mast cell cultures, and this time-dependency was consistent with the expression kinetics of both mH4R and Fc epsilon RI. These results imply that H4R has regulatory roles in Fc epsilon RI expression and Fc epsilon RI mediated functions in mast cells. In conclusion the present study shows that H4 receptors potentially play a role in IgE induced Fc epsilon RI upregulation and in the sensitization phase but not the effector phase of mast cell degranulation. (C) 2013 Elsevier Inc. All rights reserved.