Interleukin-6 directly modulates stem cell factor-dependent development ofhuman mast cells derived from CD34(+) cord blood cells

In the present study, we attempted to clarify the effects of interleukin-6 (IL-6) on the growth and properties of human mast cells using cultured mast cells selectively generated by stem cell factor (SCF) from CD34(+) cord bl ood cells. The addition of IL-6 to cultures containing mast cells resulted in a substantial reduction of the number of progenies grown by SCF in the l iquid culture. This IL-6-mediated inhibition of mast cell growth may be due in part to the suppression at the precursor level, according to the result s of a clonal cell culture assay. Moreover, a flow cytometric analysis show ed that the cultured mast cells grown in the presence of SCF+IL-6 had decre ased c-kit expression, The exposure of cultured mast cells to SCF+IL-6 also caused substantial increases in the cell size, frequency of chymase-positi ve cells, and intracellular histamine level compared with the values obtain ed with SCF alone, The flow cytometric analysis showed low but significant levels of expression of IL-6 receptor (IL-6R) and gp130 on the cultured mas t cells grown with SCF, The addition of either anti-IL-6R antibody or anti- gp130 antibody abrogated the biological functions of IL-6, Although IL-4 ex erted an effect similar to that of IL-6 on the cultured mast cells under st imulation with SCF, the results of comparative experiments suggest that the two cytokines use different regulatory mechanisms, Taken together, the pre sent findings suggest that IL-6 modulates SCF-dependent human mast cell dev elopment directly via an IL-6R-gp130 system. (C) 1999 by The American Socie ty of Hematology.