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Interleukin-4 Promotes the Development of Tryptase and Chymase
Double-Positive Human Mast Cells Accompanied by Cell Maturation
Hano Toru,
Mitsuoki Eguchi,
Ryoji Matsumoto,
Makoto Yanagida,
Junichi Yata, and
Tatsutoshi Nakahata
From The Department of Pediatrics, School of Medicine, Tokyo Medical
and Dental University, Tokyo, Japan; The Second Department of
Pediatrics, Dokkyo University School of Medicine, Tochigi, Japan; The
Department of Bacterial Infection, The Institute of Medical Science,
The University of Tokyo, Tokyo, Japan; The Pharmaceutical Development
Laboratory, Kirin Brewery Co, Ltd, Gumma, Japan; The Department of
Clinical Oncology, The Institute of Medical Science, The University of
Tokyo, Tokyo, Japan.
Human cultured mast cells (HCMCs) grown from cord blood mononuclear
cells in the presence of stem cell factor (SCF) and interleukin-6 (IL-6) expressed tryptase but no or low chymase in their cytoplasm. The
addition of IL-4 to these cells strikingly increased chymase expression. Consequently, the activity of chymase was significantly higher in IL-4-treated mast cells than that in IL-4-nontreated mast
cells, whereas the activity of tryptase and histamine content were
comparable in both cells. Electron microscopic immunocytochemistry also
showed that secretary granules containing chymase increased in
IL-4-treated mast cells. Interestingly, the IL-4-induced increase of
chymase expression in HCMCs was accompanied by morphological maturation
of the cells. Cytoplasmic projections were few in IL-4-nontreated HCMCs, and a small number of secretary granules were observed, most of
which were empty or partially filled with discrete scrolls with rough
particles showing immaturity. In contrast, IL-4-treated HCMCs had
extremely abundant cytoplasmic projections and had many secretary
granules filled with electron-dense crystal materials. Taken together,
immature HCMCs grown only with SCF and IL-6 expressed tryptase with no
or a low amount of chymase, and addition of IL-4 promoted cell
maturation together with the expression of both tryptase and a high
amount of chymase. Our findings will raise a possibility of a linear
pathway of human mast cell development from tryptase single positive
mast cells into tryptase and chymase double positive mast cells as the
cells mature and will suggest that this maturation process is promoted
by IL-4.
Blood, Vol. 91 No. 1 (January 1), 1998:
pp. 187-195
© 1998 by The American Society of Hematology.
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