Potential Role of Interleukin-25/Interleukin-33/Thymic Stromal Lymphopoietin-Fibrocyte Axis in the Pathogenesis of Allergic Airway Diseases / 中华医学杂志(英文版)

Objective@#Allergic airway diseases (AADs) are a group of heterogeneous disease mediated by T-helper type 2 (Th2) immune response and characterized with airway inflammation and remodeling, including allergic asthma, allergic rhinitis, and chronic rhinosinusitis with allergic background. This review aimed to discuss the abnormal epithelial-mesenchymal crosstalk in the pathogenesis of AADs.@*Data Sources@#Articles referred in this review were collected from the database of PubMed published in English up to January 2018.@*Study Selection@#We had done a literature search using the following terms "allergic airway disease OR asthma OR allergic rhinitis OR chronic sinusitis AND IL-25 OR IL-33 OR thymic stromal lymphopoietin OR fibrocyte". Related original or review articles were included and carefully analyzed.@*Results@#It is now believed that abnormal epithelial-mesenchymal crosstalk underlies the pathogenesis of AADs. However, the key regulatory factors and molecular events involved in this process still remain unclear. Epithelium-derived triple cytokines, including interleukin (IL)-25, IL-33, and thymic stromal lymphopoietin (TSLP), are shown to act on various target cells and promote the Th2 immune response. Circulating fibrocyte is an important mesenchymal cell that can mediate tissue remodeling. We previously found that IL-25-circulating fibrocyte axis was significantly upregulated in patients with asthma, which may greatly contribute to asthmatic airway inflammation and remodeling.@*Conclusions@#In view of the redundancy of cytokines and "united airway" theory, we propose a new concept that IL-25/IL-33/TSLP-fibrocyte axis may play a vital role in the abnormal epithelial-mesenchymal crosstalk in some endotypes of AADs. This novel idea will guide potential new intervention schema for the common treatment of AADs sharing common pathogenesis in the future.

Crystalline Silica Promotes Rat Fibrocyte Differentiation in Vitro, and Fibrocytes Participate in Silicosis in Vivo / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>The aim of this study was to investigate the effects of SiO2 on fibrocytes and whether fibrocytes participate in silicosis in vivo.</p><p><b>METHODS</b>A macrophagocyte (AM)/fibrocyte coculture system was established, and AMs were treated with 100 μg/mL SiO2. Flow cytometry was used to detect the number of fibrocytes. Real-time PCR was performed to measure the expression of collagen I, collagen III, and α-SMA mRNA. The levels of collagen I, collagen III, and TGF-β1 protein were determined by ELISA. Immunohistochemical staining was performed to measure α-SMA protein expression. A rat silicosis model was induced by intratracheal instillation of SiO2. Lung histopathological evaluation was conducted using HE and Masson's trichrome staining after 1 and 9 weeks. The number of fibrocytes in peripheral blood or lung tissue of rat was detected by flow cytometry. Double-color immunofluorescence was applied to identify fibrocytes in the lung tissue.</p><p><b>RESULTS</b>Peripheral blood monocytes were found to differentiate into fibrocytes in vitro in a time-dependent manner, and exposure to crystalline silica might potentiate fibrocyte differentiation. In addition, fibrocytes were able to migrate from peripheral blood to the lung tissue, and the number of fibrocytes was increased after SiO2 exposure.</p><p><b>CONCLUSION</b>Silica exposure potentiates fibrocyte differentiation, and fibrocytes may participate in silicosis in vivo.</p>

Cells and cellular interactions in the pathogenesis of idiopathic pulmonary fibrosis / 医学研究生学报

Idiopathic pulmonary fibrosis ( IPF) is a kind of Interstitial lung disease with cause unknown,which is aggressive for its increasing prevalence and high morbidity and mortality.At present the pathogenesis of IPF is not entirely clear, but cells and cel-lular interactions play a decisive role on the alveolar inflammation and fibrosis results.We review IPF related cells of interest ( immune competent cells and fibroblast, fibrocyte, myofibroblast, endothelial and alveolar epithelial cells) , to summarize cells and cellular in-teractions in the pathogenesis of IPF,and discuss new research directions and therapeutic targets.

Peripheral blood fibrocytes: new information to explain the dynamics of Leishmania infection

Fibrocytes are important for understanding the progression of many diseases because they are present in areas where pathogenic lesions are generated. However, the morphology of fibrocytes and their interactions with parasites are poorly understood. In this study, we examined the morphology of peripheral blood fibrocytes and their interactions with Leishmania (L.) amazonensis . Through ultrastructural analysis, we describe the details of fibrocyte morphology and how fibrocytes rapidly internalise Leishmania promastigotes. The parasites differentiated into amastigotes after 2 h in phagolysosomes and the infection was completely resolved after 72 h. Early in the infection, we found increased nitric oxide production and large lysosomes with electron-dense material. These factors may regulate the proliferation and death of the parasites. Because fibrocytes are present at the infection site and are directly involved in developing cutaneous leishmaniasis, they are targets for effective, non-toxic cell-based therapies that control and treat leishmaniasis.

Establishment and identification of induced pluripotent stem cells in liver cancer patients

OBJECTIVE@#To induce pluripotent stem (IPS) cells from fibrocytes that are separated from liver cancer patients.@*METHODS@#The fibrocytes were reprogrammed to IPS cells by lentiviral vector, stained and identified by immunohistochemistry.@*RESULTS@#The IPS cells were successfully established from fibrocytes after infection, and IPS cell clones formed in round shape under a microscopy. The induction rate was 0.013%±0.007%. No tumor formed at the back of nude mice within 8 weeks after the inoculation of cell clones. However, tetatoma appeared in nude mice within 1 week after IPS inoculation. A few tumors formed in nude mice within 4 weeks after the inoculation of cell clones. However, subcutaneous tumors formed within 1 week after IPS inoculation. The induced IPS cells showed three germ layers in tetatoma. Nanog and OCT4 in the induced IPS cells showed hypomethylation. SSEA-A, TRA-1-6-, TRA-1-81 and Nanog were highly expressed in the induced IPS cells, indicating the IPS cells possessed the similar ability as the stem cells.@*CONCLUSIONS@#The IPS cells of liver cancer patients can be established effectively from fibrocytes and can be cultured stably in vitro, which provides an approach for the treatment of intermediate or advanced stage liver cancer.

Research on CXCL12/CXCR4 biological axis and idiopathic pulmonary fibrosis / 中国药理学通报

Idiopathic pulmonary fibrosis(IPF), with unknown pathogeny, is an interstitial lung disease.The pathological features are diffuse epithelial-cell lesion, fibroblast proliferation, myofibroblast differentiation and excessive extracellular matrix deposition.CXCR4 is the predominant chemokine receptor on fibrocytes;CXCL12 is the only ligand of CXCR4.A large number of studies have shown that CXCL12/CXCR4 biological axis plays an important role in the pathogenesis of idiopathic pulmonary fibrosis.Under the regulation of hypoxia, HIF-1α and PI3K-Akt-mTOR path, CXCL12/CXCR4 biological axis promotes lung fibroblast proliferation, myofibroblast differentiation and extracellular matrix deposition, resulting in development and progression of IPF.

Morphological Changes of Retinal Pigment Epithelium After Experimental Retinal Detachment

After the rhegmatogenous retinal detachment was induced experimentally in the rabbit eyes, ultrastructural changes in the retinal pigment epithelium (RPE) were studied with electron microscope. After 3 days of retinal detachment, apical portion of the retinal pigment epithelium was mounded and apical processes were shortened, widened and reduced in number. In other areas proliferative changes were observed in the RPE and some of the proliferated cells migrated into the vitreal space. These changes were more progressed with time. Three weeks after retinal detachment, there were areas of fibroblast-like cells proliferation with production of collagen fibers. From the evidence of cell junctions, melanin granules in the Cytoplasm and basement membrane formation, proliferated fibroblast-like cells were thought to be originated from the RPE cells.

STUDY ON ULTRASTRUCTURE OF THE FIBROBLASTS / 解剖学报

Male Wistar rats were used to investigate the ultrastructure of the fibroblasts. The animals were sacrified at several time intervals after the collodion tubules were embedded subscutaneously on the backs, and the materials taken from the connective tissues around the collodion tubules were observed by light and electron microscopy. Six basic types of fibroblasts (little-differentiated fibroblast, young fibroblast, collagenoblast, myofibroblast, fibroclast and fibrocyte) were studied ultrastructurally. In each of its three phases (prophase, metaphase and telophase), the collagenoblast showed different functional conditions. The fibroclasts contain two subtypes, the phagocytosis and the lysosome subtypes, the former phagocytosing the collagen fibrils with a characteristic crossing banding and the latter phagocytosing the collagen fibrils which had been cleaved by the collagenase. The fibrocytes consist probably of two subtypes, the resting and aging subtypes. The observations demonstrate that the fibroblasts were derived from undifferentiated cells around capillaries and the little-differentiated fibroblasts are the youngest cell type of all fibroblasts. The collagenoblasts and fibroclasts are the main cells responsible for collagen biosynthesis and collagen degradation respectively. In the present paper a new concept, the "The Fibroblast System", has been proposed, which includes the six basic types of fibroblasts and there are not only structural but also functional relationships among them.

ISOLATION AND IDENTIFICATION OF CIRCULATING FIBROCYTES FROM HUMAN PERIPHERAL BLOOD / 解剖学报

Objective To establish an effective method of isolating and culturing circulating fibrocytes from human peripheral blood and study the relationship between the expression specific molecule markers expression and the morphological characteristics. Methods Total peripheral blood leukocytes were isolated from human peripheral blood by being centrifuged over Ficoll-Paque and cultured in DMEM supplemented with 20% fetal calf serum.Adhered cells were detected with immunocytochemistry,FCM and electron microscopy.The collagen synthesis was studied by measurement of the hydroxyproline concentration in the medium with chemical method. Results After 9 days cultue in vitro,CD34,CD45 and collagen Ⅰ staining was positive and 83.5% of these cells secreted collagen Ⅰ detected by FCM.Electron microscopy of circulating fibrocytes showed morphological characteristics of fibroblasts.The hydroxyproline concentration in the medium was 11.17%mg/L,which was statistically and significantly different compared with 8.07mg/L in the control medium(P