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Neutralizing Endogenous IL-6 Renders Mast Cells of the MC_T Type from Lung, but Not the MC_TC Type from Skin and Lung, Susceptible to Human Recombinant IL-4-Induced Apoptosis ¹

Carole A. Oskeritzian^*, Wei Zhao^*, Andrea L. Pozez, Neri M. Cohen, Margaret Grimes and Lawrence B. Schwartz^2,*

Departments of ^* Internal Medicine, Surgery, and Pathology, Virginia Commonwealth University, Richmond, VA 23298

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 MC_T phenotype from rhIL-4-mediated apoptosis, because neutralization of IL-6 renders these mast cells sensitive. In contrast, mast cells of the MC_TC phenotype from skin and lung were resistant to IL-4-mediated apoptosis, even after neutralization of endogenous IL-6. MC_TC cells were CD124^low, whereas those of the MC_T cells were CD124^high. These observations extend the phenotypic differences between MC_T and MC_TC types of human mast cells to include different functional responses to IL-4.

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