Study On Recruitment And Correlated Signal Of Fibrocytes In Lung Of Idiopathic Pulmonary Fibrosis

Background and ObjectiveIdiopathic Pulmonary Fibrosis(IPF) is the most common category of idiopathic interstitial pneumonias. The incidence of IPF seems to be increasing. The real mechanisms underlying the development of IPF still remain unknown. The pathologic hallmarks of IPF are Fibroblastic Foci, which are areas rich in mesenchymal cells and Extracellular Matrix (ECM). These Fibroblastic Foci, which consist of fibroblasts and myofibroblasts cell, are deemed to be a key element in the diagnosis of IPF. Fibrocytes have been suggested that they are a potential source of formation of myofibroblast. They co-express the common leukocyte antigen CD45, the hematopoietic stem cell antigen CD34, and mesenchymal markers such as Collagen-I, fibronectin, a-smooth muscle actin(a-SMA) and prolyl-4-hydroxylase. Most of them express the receptor CXCR4 supporting the concept that the CXCR4/CXCL12 pathway may be important for tissue recruitment. So far, fibrocytes have not been demonstrated in the lungs of patients with IPF or other human interstitial lung diseases.The present study is designed in order to define the following points:to observe that there have fibrocytes in human lung tissue by immunofluorescence; fibrocytes are observed in lung tissues with combinations including CXCR4 or CD34 or CD45RO with mesenchymal markers; to analyze correlation of fibrocytes of different staining combination; to evaluate the effect of CXCR4/CXCL12 signal pathway on recruiting of fibrocytes and expansion of the fibroblast/myofibroblast population in IPF by immunofluorescence. The aim of our study is to evaluate the role of fibrocytes for the pathogenesy of IPF, and to provide evidence of molecular biology for better understanding evolution and development of IPF and potential therapeutic target of IPF.Materials and methods20 lung tissues were collected by open lung biopsies from patients with IPF. Lung tissue samples of the control group obtained from 20 patients undergoing thoracotomy for bronchiectasis. Patients in the control group had no other underlying lung disease and the specimens distanced 5 cm from the affections.The histologic diagnosis in these specimens was normal lung tissue. To observe that there have fibrocytes in lung tissue by immunofluorescence. Four groups respectively are①CXCR4/Collagen-Ⅰ,②CD34/a-SMA,③CD34/Collagen-Ⅰ,④CD45RO/Collagen-Ⅰby special cell surface markers. The numble of the double positive cell of four groups of all lung tissue samples is detected respectively by immunofluorescence.These dates are analysed by statistical software SPSS 12.0. Differences between the number of fibrocytes detected in lungs tissue samples are compared by using Kruskal-Wallis test and Mann-Whitney u test, a=0.05 is considered as the level of tests.ResultFibrocytes have been identified in tissues in 19 out of 20 IPF and not identified in lung of control group by immunofluorescence.The number of four groups in lung of IPF respectively is (5.19±0.0152%), (2.19±0.0083%), (2.56±0.0109%), (2.29±0.0082%).Compared with others, the number of the double positive cell expressing for CXCR4/Collagen-I is much higher.(P< 0.001).Conclusion1. This study suggests that fibrocytes existed in the lung tissue of patients with IPF, but fibrocytes did not exist in lung of control group. Fibrocytes may facilitate to the expansion of the fibroblast/myofibroblast population in IPF.2. Our study suggests that fibrocytes have been demonstrated in the lungs of patients with IPF or other human interstitial lung diseases.3.There have more CXCR4 positive fibrocytes in lung of IPF, these findings indicate that these fibrocytes have been likely recruited through the CXCR4/CXCL12 axis, and may play a important role in evolution and development of IPF.