Cultured human intestinal mast cells express functional IL-3 receptors and respond to IL-3 by enhancing growth and IgE receptor-dependent mediator release.

Abstract

Mast cells are immunoregulatory effector cells capable of releasing different mediators and cytokines implicated in inflammatory tissue processes. Previous studies suggested that IL-3 regulates growth and function of murine mast cells and human mast cell precursors, but does not affect mature human mast cells. In the present study, we found expression of IL-3 receptors (IL-3R) in freshly isolated human intestinal mast cells by reverse transcriptase (RT)-PCR and in mast cells cultured with stem cell factor (SCF) using RT-PCR and flow cytometry. IL-3R expression was enhanced when the culture medium was supplemented with IL-4 in addition to SCF. In the presence of SCF, IL-3 significantly enhanced mast cell growth in a dose-dependent fashion (179+/-51% of control, p</=0.004, n=9, ED(50) approximately 15 ng/ml) by decreasing mast cell apoptosis rather than inducing proliferation. Furthermore, IL-3 selectively enhanced histamine (from 39.6+/-12.4 to 51.2+/-15.7% specific release, p<0.02, n=8) and leukotriene C(4) (LTC(4), 5.1+/-3.4 to 10.8+/-5.5 ng/10(6) mast cells, p<0.03, n=6) release triggered by IgE receptor cross-linking without affecting prostaglandin D(2) production. In conclusion, our data show that human intestinal mast cells express functional IL-3R, indicating that IL-3 not only regulates growth and function of immature, but also that of mature human mast cells.