透過您的圖書館登入
IP:18.218.145.131
  • 學位論文

氣喘病人周邊Fibrocyte之研究

Study on the circulating fibrocyte in the patients with asthma

指導教授 : 孫昭玲

摘要


前言:Fibrocytes是修復傷口、組織重整的重要血液細胞,在慢性氣喘中可能扮演重要角色,但詳細致病機制的研究尚未清楚,因此本研究探討Fibrocytes與人類氣喘疾病之相關性,和其生長調控之情形。 實驗方法:建立多色流式細胞技術,分析人類周邊血之Fibrocytes的比例,與氣喘病人指標之相關性。另外利用人類TGF-β和TGF-β RI inhibitor SB 431542,了解Fibrocytes分化和生長情形。 結果:將CD3-CD19-CD45+Collagen+PM-2K-細胞定義為Fibrocytes,發現氣喘病人周邊血中Fibrocytes的比例高於正常人,而Macrophages比例則在氣喘病人較低,且Fibrocytes與Macrophages比例呈負相關。另外氣喘病人之Fibrocytes比例和IgE濃度有顯著的正相關。在正常人中,CD14+ monocytes所分化的Fibrocytes,其分化與生長受到TGF-β RI inhibitor-SB 431542的抑制,但受到人類TGF-β的促進。 結論:本研究幫助了解氣喘病人血液中Fibrocytes之比例與氣喘疾病的相關性,可作為了解肺部組織重整及纖維化的重要研究依據。

關鍵字

氣喘

並列摘要


Background: Fibrocytes are bone marrow-derived cells for wound repair and tissue remodeling which play a key role in asthma. But as the study of disease mechanism is still unclear, this study is to investigate the relationship between fibrocytes and asthma, as well as the condition of its growth regulation. Methods: To set up the method of multiparametric flow cytometry to analyze percentages of fibrocytes in human peripheral blood, and examine the relationship between fibrocytes and clinical parameters in asthma patients. Using human recombinant TGF-β and TGF-β RI inhibitor SB 431542 to examine the signaling involved in fibrocyte differentiation and growth. Results: We defined CD3-CD19-CD45+Collagen+PM-2K- cells as fibrocytes, and found that the percentages of circulating fibrocytes in asthma patients were significantly higher than healthy controls, but macrophage percentages were significantly lower than healthy controls. In addition, fibrocyte percentages were negatively correlated with macrophage percentages and positively correlated with IgE level in asthma patients. In healthy controls, the differentiation and growth of fibrocytes from CD14+ monocytes were inhibited by TGF-β RI inhibitor SB 431542 and promoted by human recombinant TGF-β. Conclusions: This study contributes to an understanding for the association of fibrocyte in the disease activity of asthma. This study will be the important basis for studying lung remodeling and fibrosis.

並列關鍵字

asthma fibrocyte

參考文獻


1. Bucala R, Spiegel LA, Chesney J, Hogan M, Cerami A. 1994. Circulating fibrocytes define a new leukocyte subpopulation that mediates tissue repair. Mol Med 1: 71-81
2. Phillips RJ, Burdick MD, Hong K, Lutz MA, Murray LA, Xue YY, Belperio JA, Keane MP, Strieter RM. 2004. Circulating fibrocytes traffic to the lungs in response to CXCL12 and mediate fibrosis. J Clin Invest 114: 438-46
3. Abe R, Donnelly SC, Peng T, Bucala R, Metz CN. 2001. Peripheral blood fibrocytes: differentiation pathway and migration to wound sites. J Immunol 166: 7556-62
4. Chesney J, Metz C, Stavitsky AB, Bacher M, Bucala R. 1998. Regulated production of type I collagen and inflammatory cytokines by peripheral blood fibrocytes. J Immunol 160: 419-25
5. Hartlapp I, Abe R, Saeed RW, Peng T, Voelter W, Bucala R, Metz CN. 2001. Fibrocytes induce an angiogenic phenotype in cultured endothelial cells and promote angiogenesis in vivo. FASEB J 15: 2215-24

延伸閱讀