Neutralizing Endogenous IL-6 Renders Mast Cells of the MCT Type from Lung, but Not the MCTC Type from Skin and Lung, Susceptible to Human Recombinant IL-4-Induced Apoptosis

Abstract

Human cord blood-derived mast cells undergo apoptosis upon exposure to recombinant human (rh)IL-4 and become resistant to rhIL-4-induced apoptosis when cultured in the presence of rhIL-6. The current study extends these effects of rhIL-4 to different populations of human mast cells, namely fetal liver-derived mast cells, lung-derived mast cells, and skin-derived mast cells. Endogenous production of IL-6 appears to protect fetal liver-derived mast cells and those of the MCT phenotype from rhIL-4-mediated apoptosis, because neutralization of IL-6 renders these mast cells sensitive. In contrast, mast cells of the MCTC phenotype from skin and lung were resistant to IL-4-mediated apoptosis, even after neutralization of endogenous IL-6. MCTC cells were CD124low, whereas those of the MCT cells were CD124high. These observations extend the phenotypic differences between MCT and MCTC types of human mast cells to include different functional responses to IL-4.