EFFECTS OF T-HELPER 2-TYPE CYTOKINES, INTERLEUKIN-3 (IL-3), IL-4, IL-5, AND IL-6 ON THE SURVIVAL OF CULTURED HUMAN MAST-CELLS

Although stem cell factor (SCF) has been identified as a critical cyto kine for the development of human mast cells from their progenitors, t he effects of other cytokines on human mast cells are less well unders tood. We examined the effects of several cytokines on the survival of human mast cells of 100% purity generated in suspension cultures of um bilical cord blood mononuclear cells in the presence of 100 ng/mL reco mbinant human (rh) SCF and interleukin-6 (IL-6). Mast cells suspended in conventional serum-containing medium died over a period of 2 to 6 d ays after the withdrawal of SCF and IL-6. The cells became pyknotic an d underwent DNA fragmentation characteristic of apoptosis. The additio n of SCF, IL-3, IL-4, IL-5, or IL-6 to the cultures in both serum-cont aining and serum-free medium prolonged their survival in a dose-depend ent manner. Some other cytokines, such as IL-2, IL-9. IL-10, IL-11, tu mor necrosis factor-alpha, transforming growth factor-beta 1, and nerv e growth factor, had no survival-promoting effect at 100 ng/mL. Preinc ubation of mast cells with SCF, IL-4, IL-5, or IL-6 for 24 hours durin g sensitization with IgE enhanced IgE/anti-IgE antibody-induced histam ine release from mast cells, whereas IL-3 showed a negligible effect. Polymerase chain reaction amplification of alpha-chains of IL-3 recept or (R), IL-4 R, IL-5 R, and IL-6 R yielded products of the correct siz e predicted from the sequence of each receptor. The binding assay usin g I-125-labeled IL-3 indicated that these mast cells bear receptors fo r IL-3. These findings suggest that IL-3, IL-4, IL-5, and IL-6, which are mainly produced by T-helper 2 lymphocytes, might regulate the func tions of human mast cells in vivo via specific receptors in allergic r eactions. (C) 1995 by The American Society of Hematology.