COMPARATIVE CYTOKINE RELEASE FROM HUMAN MONOCYTES, MONOCYTE-DERIVED IMMATURE MAST-CELLS, AND A HUMAN MAST-CELL LINE (HMC-1)

To obtain further information regarding the role of cytokines during m ast cell differentiation, we have investigated changes of cytokine sec retion in mast cells developing from the human peripheral blood monocy tic cell fraction during culture with fibroblast-derived conditioned m edia. The influence of stem cell factor and an antibody to the respect ive receptor in our culture system was studied as well. Interleukin (I L)-1 alpha, IL-1 beta, IL-6, and tumor necrosis factor (TNF)alpha were spontaneously secreted by cultured cells at day 1 and decreased marke dly by day 14. Similar changes occurred also during culture with stem cell factor and were partially abrogated by an anti-receptor antibody. IL-8 was secreted at a high level throughout the culture, whereas no spontaneous secretion of IL-2, IL-3, IL-4, and IL-7 was measured at al l. Upon stimulation with phorbol myristate acetate and A23187, culture d cells showed substantially more release of IL-3 and TNF-alpha after 14 d of culture, compared to peripheral blood monocytic cells. Preform ed TNF-alpha was found in one of three monocytic cell preparations fro m peripheral blood, but not in monocytic cell-derived mast cells. Duri ng mast cell differentiation, cytokines from monocytic cells are there fore downregulated while the cells assume a pattern typically found in mast cells.