1. ¹Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan
2. ²Division of Molecular and Cellular Biology, Department of Molecular Oncology, Institute on Aging and Adaptation, Shinshu University Graduate School of Medicine, Matsumoto, Japan
3. ³Biomembrane Signaling Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan
4. ⁴Institute for Biosciences, School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women's University, Nishinomiya, Japan
5. ⁵Research Complex for the Medicine Frontiers, Aichi Medical University, Nagakute, Japan
6. ⁶Department of Immunobiology, School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women's University, Nishinomiya, Japan

Correspondence: Dr Satoshi Tanaka, PhD, Department of Immunobiology, School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women's University, Kyuban-cho 11-68, Koshien, Nishinomiya, Hyogo 663-8179, Japan. E-mail: s_tanaka@mukogawa-u.ac.jp

Received 4 September 2008; Revised 30 October 2008; Accepted 4 November 2008; Published online 9 February 2009.

Abstract

By using the recently established culture system that reproduces the terminal differentiation process of connective tissue-type mast cells, we found significant transcriptional induction of CD44. As CD44 is a primary receptor for hyaluronan (HA), which is one of the major extracellular matrix components, we investigated the role of CD44 in cutaneous mast cells. When co-cultured with fibroblasts, mouse bone marrow-derived cultured mast cells (BMMCs) were found to form clusters in an HA-dependent manner. As compared with BMMCs derived from the wild-type mice, those from the CD44^-/- mice exhibited impaired growth during the co-cultured period. Furthermore, in the peritoneal cavities and ear tissues, mature mast cells were fewer in number in the CD44^-/- mice than in the wild-type mice. We investigated roles of CD44 in mast cell proliferation by reconstituting BMMCs into the tissues of mast cell-deficient, Kit^W/Kit^W-v mice, and found that the number of metachromatic cells upon acidic toluidine blue staining in the tissues transplanted with CD44^-/- BMMCs was not significantly changed for 10 weeks, whereas that in the tissues transplanted with the CD44^+/+ BMMCs was significantly increased. These results suggest that CD44 plays a crucial role in the regulation of the cutaneous mast cell number.