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Stem Cell Factor Has a Suppressive Activity to IgE-Mediated Chemotaxis of Mast Cells¹

Junko Sawada^*, Shinya Shimizu, Takuya Tamatani^,, Shiro Kanegasaki, Hirohisa Saito^¶, Akane Tanaka^*, Naotomo Kambe^||, Tatsutoshi Nakahata^# and Hiroshi Matsuda^2,*

^* Laboratory of Molecular Pathology and Therapeutics, Division of Animal Life Science, Graduate School, Institute of Symbiotic Science and Technology, Tokyo University of Agriculture and Technology, Tokyo, Japan; Department of Immunology, National Institute of Animal Health, Tsukuba, Japan; Effector Cell Institute, Research Center for Advanced Science and Technology, University of Tokyo, Tokyo, Japan; Research Center for Advanced Science and Technology, University of Tokyo, Tokyo, Japan; ^¶ Department of Allergy and Immunology, National Research Institute for Child Health and Development, Tokyo Japan; and Departments of ^|| Dermatology and ^# Pediatrics, Kyoto University Graduate School of Medicine, Kyoto, Japan

Stem cell factor (SCF), which is well known as a cytokine capable of amplifying development and functions of mast cells, is mainly released from fibroblasts in the peripheral tissue. To investigate whether SCF controlled chemotactic migration of mast cells induced by IgE-specific Ag, murine bone marrow-derived cultured mast cells (BMCMC) and human cord blood-derived cultured mast cells (HuCMC) were preincubated with SCF. Although BMCMC and HuCMC sensitized with IgE directly moved toward specific Ag, preincubation for even 1 h with an optimal dose of SCF suppressed the IgE-mediated chemotactic movement. No or little inhibitory effect of SCF was detected in BMCMC derived from c-kit receptor-defect WBB6F₁-W/W^v mice. In contrast, preincubation of BMCMC and HuCMC with SCF enhanced -hexosaminidase release and Ca²⁺ mobilization in response to Ag after sensitization with IgE. Using the real-time record of chemotactic migration, BMCMC preincubated with SCF manifested motionless without degranulation. These results suggest that locally produced SCF may have an inhibitory effect on chemotaxis of mast cells, contributing to their accumulation and enhancement of functions at the peripheral site in allergic and nonallergic conditions.

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