Mutual reactions of human mast cells and fibroblasts in the regulation of remodering processof allergic inflammation

人肥大细胞与成纤维细胞的相互作用在调节过敏性炎症重塑过程中的作用

• 批准号: 08457235
• 负责人: MIYACHI Yoshiki
• 金额: $ 4.74万
• 依托单位: KYOTO UNIVERSITY (1998)Gunma University (1996-1997)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08457235/
• 关键词: Mast cells; Allergic inflammation; Fibroblasts; Remodeling; Growth factors; Fibrosis; ヒト肥満細胞

Two types of human mast cells have been recognized based on their content of neutral proteases ; MCT cells containing tryptase and MCTC cells containing both tryptase and chymase. Cultured human mast cells raised from umbilical cord blood cells are successfully switched from MCT cells to MCTC cells. The human mast cell is capable of releasing proteases as well as cytokines to initiate and maintain a cutaneous allergic inflammation. Furthermore, the co-culture of human mast cells with dermal fibroblasts revealed the mutual cell biological effects such as fibroblast proliferation as well as collagen production. Also, activated mast cells generate TGF-b and bFGF suggesting the important roles of mast cells in the remodeling process of allergic inflammation, which may play important roles in cutaneous fibrosis such as hypertrophic scar and scieroderma. These findings indicate that the interaction of human mast cells and fibroblasts may be critical in the regulation of fibrotic rcutaneous emodeling. Taken together, the regulation of mast cell activation in allergic inflammatory skin diseases should be promising for the therapeutic approaches in dermatology.

根据中性蛋白酶的含量，已经识别出两种类型的人肥大细胞；含有胰蛋白酶的MCT细胞和同时含有胰蛋白酶和乳糜酶的MCTC细胞。从脐带血细胞培养的人肥大细胞成功地从MCT细胞转化为MCTC细胞。人类肥大细胞能够释放蛋白酶和细胞因子来启动和维持皮肤过敏性炎症。此外，人类肥大细胞与真皮成纤维细胞共培养显示出成纤维细胞增殖和胶原生成等相互细胞生物学效应。激活的肥大细胞产生TGF-b和bFGF，提示肥大细胞在变应性炎症的重塑过程中发挥重要作用，可能在增生性瘢痕、硬皮病等皮肤纤维化中发挥重要作用。这些发现表明，人类肥大细胞和成纤维细胞的相互作用可能在纤维化皮肤模型的调节中起关键作用。综上所述，肥大细胞活化在过敏性炎症性皮肤病中的调节应该是有希望的皮肤病治疗方法。

项目成果

Motohiro Kurosawa: "Effect of mast cell-derived mediators and mast cell-related nuetral proteases on human dermal fibroblast proliferation and type I collagen production" J Allergy Clin Immunol,. in press.

Motohiro Kurosawa：“肥大细胞衍生介质和肥大细胞相关中性蛋白酶对人真皮成纤维细胞增殖和 I 型胶原蛋白产生的影响”J Allergy Clin Nutrition，。

黒沢元博: "分子アレルギー学" メディカルレビュー社, 600 (1998)

黑泽元宏：《分子过敏》医学评论出版，600（1998）

Masatoshi Abe, Motohiro Kurosawa, Osamu Ishikawa, Yoshiki Miyachi, Hiroshi Kido: "Mast cell tryptase stimulates both human dermal fibroblast proliferation and type I collagen production." Clin Exp Allergy. 28. 1509-1517 (1998)

Masatoshi Abe、Motohiro Kurosawa、Osamu Ishikawa、Yoshiki Miyachi、Hiroshi Kido：“肥大细胞类胰蛋白酶刺激人真皮成纤维细胞增殖和 I 型胶原蛋白产生。”

Motohiro Kurosawa: "Heterogeneity of mast cells in mastocytosis and inhibitory effects of ketotifene and ranitidine on the mediators in an indolent systemic mastocytosis." J Allergy Clin Immunol. (in press).

Motohiro Kurosawa：“肥大细胞增多症中肥大细胞的异质性以及酮替芬和雷尼替丁对惰性系统性肥大细胞增多症介质的抑制作用。”

Motohiro Kurosawa: "Heterogeneity of mast cells in mastocytosis and inhibitory effects of ketotifene and ranitidine on the mediators in an indolent systemic mastocytosis." J Allergy Clin Immumol. 100. S25-S32 (1997)

Motohiro Kurosawa：“肥大细胞增多症中肥大细胞的异质性以及酮替芬和雷尼替丁对惰性系统性肥大细胞增多症介质的抑制作用。”