Effects of IL-3 and IL-4 on proliferation and transdifferentiation of mast cells

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There are two phenotypically distinct subpopulatins of mast cells : connective tissue-type mast cells (CTMC) and mucosal mast cells(MMC). These populations differ in their location, cell sizu, staining characteristics, mediator content and factor dependency. Although proliferation of MMC was known to be T cell dependent in vivo and thought to be interleukin 3(IL-3) dependent in vitro, the factors on which CTMC proliferation depends remained elusive. We recently found that mature CTMC separated from mouse peritoneal cells could proliferate extensively in methylcellulose culture and maintain the appearance and function of CTMC (Nature 1986).In this study, we have indicated that clonal growth of CTMC could not be induced by IL-3 alone and required the presence of both IL-3 and interleukin 4 (IL-4). We also tested whether IL-3 can act co-stimulator for CTMC proliferation in the compinations with various phorbol derivatives. Neither IL-3 nor 12-0-tetradecanoylphorbol-13 acetate(TPA) stimulated mast cell colony growth from BDF_1 mice peritoneal CTMC purified by percoll density-gradient centrifugation. However, when IL-3 and TPA were supplemented simultaneously in the culture, numerous CTMC-type mast cell colonies developed. Other 3 phorbol derivatives, which are capable of activating protein kinase C (PKC), also induced proliferation of CTMC in the presence of IL-3, but other 3 phorbol derivatives, all of which are unable to activate PKC, failed to induce the coliny growth. Continuous presence of IL-3 and TPA in culture was required for extensive proliferation of CTMC. These results indicate that activation of PKC may act inportant role to induce the proliferation of CTMC in vitro. Cytological examination of individual colonies suported by IL-3 and IL-4 suggestthe transdifferentiation from mature CTMC to alcian blue(+)-safranin(-)-Berberine(-) MMC like cells in vitro.