title: Restriction of mast cell proliferation through hyaluronan synthesis by co-cultured fibroblasts.
abstract: Appropriate culture models for tissue mast cells are required to determine how they are involved in regulation of local immune responses. We previously established a culture model for cutaneous mast cells, in which bone marrow-derived immature mast cells were co-cultured with Swiss 3T3 fibroblasts in the presence of stem cell factor. In this study, we focused on the roles of hyaluronan, which is produced by the feeder fibroblasts and forms the extracellular matrix during the co-culture period. Hyaluronan synthesis was found to be mediated by hyaluronan synthase 2 (HAS2) expressed in Swiss 3T3 cells. A decreases in the amount of hyaluronan, which was achieved by retroviral expression of short hairpin RNA for Has2 or by addition of hyaluronidase, significantly enhanced the proliferation of the cultured mast cells without any obvious effects on their maturation. Although we previously demonstrated that CD44 is required for proliferation of cutaneous mast cells, the deficiency of hyaluronan did not affect the proliferation of the cultured mast cells that lack CD44. These findings suggest that the extracellular matrix containing hyaluronan may have a potential to restrict proliferation of cutaneous mast cells in a CD44-independent manner.
authors.affiliation: Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, Kyoto University, Japan.
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Takano
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Furuta
authors.forename: Kazuhito
authors.initials: K
authors.lastname: Yamashita
authors.forename: Mariko
authors.initials: M
authors.lastname: Sakanaka
authors.forename: Naoki
authors.initials: N
authors.lastname: Itano
authors.forename: Eiichi
authors.initials: E
authors.lastname: Gohda
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Nakayama
authors.forename: Koji
authors.initials: K
authors.lastname: Kimata
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Sugimoto
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ichikawa
authors.forename: Satoshi
authors.initials: S
authors.lastname: Tanaka
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D005347:Fibroblasts / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D014453:Glucuronosyltransferase / Q000235:genetics / Q000378:metabolism*; D018960:Hyaluronan Receptors / Q000235:genetics; D000076002:Hyaluronan Synthases; D006820:Hyaluronic Acid / Q000378:metabolism*; D008407:Mast Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D041701:Swiss 3T3 Cells
chemical_list: D018960:Hyaluronan Receptors; D006820:Hyaluronic Acid; D014453:Glucuronosyltransferase; C491099:Has2 protein, mouse; D000076002:Hyaluronan Synthases