共查询到20条相似文献,搜索用时 15 毫秒
1.
M. Toida Y. Okumura K. K. Swe Win N. Oka T. Takami R. ádány 《The Histochemical journal》1995,27(6):449-456
Summary In the present study, the distribution pattern and characteristics of cells containing Factor XIII subunita (FXIII A) have been studied in benign and malignant lesions of human buccal mucosa. Tissues from four irritation fibromas
and three squamous cell carcinomas were studied by means of double immunofluorescent staining techniques in which the detection
of FXIII A was combined with a reaction with CD14 (recognizing a monocyte/macrophage differentiation marker antigen), Mac
387 (reacting with a special subset of macrophages), anti-HLA-DR, Ki-M7 (labelling phagocytosing macrophages) or Ki-67 (visualizing
a nuclear antigen associated with cell proliferation) monoclonal antibodies. FXIII A was detected in cells of the connective
tissue stroma in both benign and malignant buccal lesions. The number of these FXIII A-reactive cells (FXIII A+ cells) increased considerably in the tumour tissues, in particular in those surrounding tumour cell clusters. FXIII A+ cells scattered in the fibromatous tissues were spindle-shaped, whereas in the tumour stroma, large stellate cells predominated,
and round cells were likewise labelled around blood vessels. FXIII A+ cells were labelled with CD14 and Ki-M7 in both fibromatous and tumoural buccal mucosa; however, they failed to show any
reaction with Ki-67. FXIII A+ cells accumulated in the tumour stroma reacted for HLA-DR as well. These results indicate that in both the benign and malignant
buccal lesions FXIII A is contained in a subpopulation of tissue macrophages, which represents a monocyte-derived (CD14+) and phagocytosing (KiM7+) cell population. The accumulation of the FXIII A+ cells in the tumour stroma is believed to be a result of direct migration from the circulating blood. The FXIII A+ cells of the tumour stroma may be actively involved in both antigen presentation and matrix remodelling during tumour progression. 相似文献
2.
Factor XIII catalyzes formation of γ-glutamyl-ε-lysyl crosslinks within fibrin clots. FXIII A2 can be activated proteolytically with thrombin and low mM Ca2+ or nonproteolytically with high monovalent/divalent cations along with low mM Ca2+. Physiologically, FXIII A2 is poised to respond to transient influxes of Ca2+ in a Na+ containing environment. A successful strategy to monitor FXIII conformational events is hydrogen–deuterium exchange (HDX) coupled with mass spectrometry. FXIII A2 was examined in the presence of different cations (Ca2+, Mg2+, Ba2+, Cu2+, Na+, TMAC+, and EDA2+) ranging from 1 to 2 mM, physiological Ca2+ concentration, to 50–500 mM for nonproteolytic activation. Increases in FXIII solvent exposure could already be observed at 1 mM Ca2+ for the dimer interface, the catalytic site, and glutamine substrate regions. By contrast, solvent protection was observed at the secondary cleavage site. These events occurred even though 1 mM Ca2+ is insufficient for FXIII activation. The metals 1 mM Mg2+, 1 mM Ba2+, and 1 mM Cu2+ each led to conformational changes, many in the same FXIII regions as Ca2+. FXIII could also be activated nonproteolytically with 500 mM tetramethylammonium chloride (TMAC+) and 500 mM ethylenediamine (EDA2+), both with 2 mM Ca2+. These different HDX studies help reveal the first FXIII segments that respond to physiological Ca2+ levels. 相似文献
3.
Summary As spontaneous abortion is a frequent finding in females with Factor XIII (FXIII) deficiency it has been presumed that this clotting factor is essential to normal pregnancy. FXIII subunit a (FXIII A) has been demonstrated in the homogenate of human uterus, but no information on its cellular distribution has been published, so far. In the present study first FXIII A was detected in paraformaldehyde-fixed, paraffin-embedded sections of human uterus by immunoperoxidase technique. Cells containing FXIII A were localized between collagen fibrils stained by Picrosirius Red F3B in the connective tissue. To characterize them the immunofluorescent detection of FXIII a was combined by the visualization of different marker antigens of monocytes and macrophages recognized by Leu-M3, RFD7, anti-HLA-DR and DAKO-anti-macrophage monoclonal antibodies on frozen sections. The coexpression of FXIII A with monocyte and macrophage differentiation marker antigens clearly proves that cells containing FXIII A in the uterus are monocyte-derived tissue macrophages. The results well agree with our previous findings demonstrating FXIII A in human monocytes and different types of macrophages. On the basis of these results, the presence of FXIII A does not seem to be a specificity of the uterus but a characteristic of monocyte/macrophage cell line including tissue macrophages, in general. 相似文献
4.
MMP-12, a macrophage-secreted elastase, is elevated in fibrotic diseases, including systemic sclerosis (SSc) and correlates with vasculopathy and fibrosis. The goal of this study was to investigate the role of MMP-12 in cardiac and cutaneous fibrosis induced by angiotensin II infusion. Ang II-induced heart and skin fibrosis was accompanied by a marked increase of vascular injury markers, including vWF, Thrombospondin-1 (TSP-1) and MMP-12, as well as increased number of PDGFRβ+ cells. Furthermore Ang II infusion led to an accumulation of macrophages (Mac3+) in the skin and in the perivascular and interstitial fibrotic regions of the heart. However, alternatively activated (Arg 1+) macrophages were mainly present in the Ang II infused mice and were localized to the perivascular heart regions and to the skin, but were not detected in the interstitial heart regions. Elevated expression of MMP-12 was primarily found in macrophages and endothelial cells (CD31+) cells, but MMP-12 was not expressed in the collagen producing cells. MMP-12 deficient mice (MMP12KO) showed markedly reduced expression of vWF, TSP1, and PDGFRβ around vessels and attenuation of dermal fibrosis, as well as the perivascular fibrosis in the heart. However, MMP-12 deficiency did not affect interstitial heart fibrosis, suggesting a heterogeneous nature of the fibrotic response in the heart. Furthermore, MMP-12 deficiency almost completely prevented accumulation of Arg 1+ cells, whereas the number of Mac3+ cells was partially reduced. Moreover production of profibrotic mediators such as PDGFBB, TGFβ1 and pSMAD2 in the skin and perivascular regions of the heart was also inhibited. Together, the results of this study show a close correlation between vascular injury markers, Arg 1+ macrophage accumulation and fibrosis and suggest an important role of MMP-12 in regulating these processes. 相似文献
5.
As spontaneous abortion is a frequent finding in females with Factor XIII (FXIII) deficiency it has been presumed that this clotting factor is essential to normal pregnancy. FXIII subunit a (FXIII A) has been demonstrated in the homogenate of human uterus, but no information on its cellular distribution has been published, so far. In the present study first FXIII A was detected in paraformaldehyde-fixed, paraffin-embedded sections of human uterus by immunoperoxidase technique. Cells containing FXIII A were localized between collagen fibrils stained by Picrosirius Red F3B in the connective tissue. To characterize them the immunofluorescent detection of FXIII A was combined by the visualization of different marker antigens of monocytes and macrophages recognized by Leu-M3, RFD7, anti-HLA-DR and DAKO-anti-macrophage monoclonal antibodies on frozen sections. The coexpression of FXIII A with monocyte and macrophage differentiation marker antigens clearly proves that cells containing FXIII A in the uterus are monocyte-derived tissue macrophages. The results well agree with our previous findings demonstrating FXIII A in human monocytes and different types of macrophages. On the basis of these results, the presence of FXIII A does not seem to be a specificity of the uterus but a characteristic of monocyte/macrophage cell line including tissue macrophages, in general. 相似文献
6.
Hemmerlein B Markus A Wehner M Kugler A Zschunke F Radzum HJ 《Cancer immunology, immunotherapy : CII》2000,49(9):485-492
Purpose: Tumor cells influence the differentiation of infiltrating macrophages. In the present study, the differentiation of macrophages
in renal cell carcinomas was investigated with special regard to their possible role in tumor growth and spread. Methods: Macrophages were characterized by means of immunohistochemistry of the Ki-M1P, 25F9, MRP8, MRP14, and MRP8/14 antigens and
by means of in situ hybridization of CSF-1, its c-fms-coded corresponding receptor, and human monocytic serine esterase-1 (HMSE-1) mRNA. Macrophage subgroups were quantified within
central tumor tissue, the corresponding tumor host interface, and tumor-free tissue and correlated with tumor necrosis, fibrosis,
and tumor stage and grade. Results: Macrophage density was much higher within tumor tissue and the tumor/host interface than in tumor-free tissue. Well-differentiated
carcinomas showed a lower degree of macrophage density than less-differentiated carcinomas. Tumor-associated macrophages could
be divided into an active inflammatory type (MRP14+, MRP8/14+) and into a late-phase inflammatory type (25F9+, MRP8+). Necrosis was seen in less-differentiated carcinomas and associated with a significantly increased density of MRP14+ macrophages, which, however, did not correlate with the extent of necrosis. The density of 25F9+ macrophages was correlated with an extensive connective tissue formation and an advanced tumor stage. c-fms, CSF-1, and HMSE-1
mRNA expression did not discriminate between the macrophage subgroups. Conclusions: Tumor-associated macrophages of the late-stage inflammatory type potentially support the spread of renal cell cancer. CSF-1
derived from tumor cells and macrophages acts as a monocyte attractant and induces macrophage differentiation able to modulate
the extracellular matrix rather than to exert cytotoxicity.
Received: 25 May 2000 / Accepted: 29 June 2000 相似文献
7.
《Biochimica et Biophysica Acta (BBA)/General Subjects》2019,1863(9):1360-1370
BackgroundRenal fibrosis is a common pathological hallmark of chronic kidney disease, and no effective treatment is clinically available to manage its progression. Astaxanthin was recently found to be anti-fibrotic, but its effect on renal fibrosis remains unclear.MethodsC57BL/6J mice were subjected to unilateral ureteral obstruction and intragastrically administered astaxanthin. Histopathology and immunohistochemistry were performed to evaluate renal fibrosis. Flow cytometry was used to examine lymphocyte accumulation in the fibrotic kidneys. Western blotting, real-time qPCR, and immunofluorescence were performed to cover the underlying mechanism concerning astaxanthin treatment during renal fibrosis.ResultsOral administration of astaxanthin effectively alleviates renal fibrosis in mice. In vitro, astaxanthin inhibited fibroblast activation by modulating Smad2, Akt and STAT3 pathways and suppressed epithelial-to-mesenchymal transition in renal tubular epithelial cells through Smad2, snail, and β-catenin. Moreover, astaxanthin significantly induced the rapid accumulation of CD8+ T cells in fibrotic kidneys, which was accompanied by elevated expression of IFN-γ. Accordingly, the depletion of CD8+ T cells strongly diminished the protective effect of astaxanthin. Further investigation showed that astaxanthin increased the population of CD8+ T cells by upregulating the expression of CCL5 in macrophages.ConclusionsThese findings highlight the beneficial effect of astaxanthin on fibroblast activation, epithelial-to-mesenchymal transition, and CD8+ T cell recruitment during renal fibrosis.General significanceThese data indicate that astaxanthin could serve as a therapeutic strategy to treat renal fibrotic conditions. 相似文献
8.
Brian W. Parks Leland L. Black Kurt A. Zimmerman Allison E. Metz Chad Steele Joanne E. Murphy-Ullrich Janusz H. Kabarowski 《Journal of lipid research》2013,54(4):1114-1123
Macrophage G2A and CD36 lipid receptors are thought to mediate efferocytosis following tissue injury and thereby prevent excessive inflammation that could compromise tissue repair. To test this, we subjected mice lacking G2A or CD36 receptor to bleomycin-induced lung injury and measured efferocytosis, inflammation, and fibrosis. Loss of CD36 (but not G2A) delayed clearance of apoptotic alveolar cells (mean 78% increase in apoptotic cells 7 days postinjury), potentiated inflammation (mean 56% increase in lung neutrophils and 75% increase in lung KC levels 7 days postinjury, 51% increase in lung macrophages 14 days postinjury), and reduced lung fibrosis (mean 41% and 29% reduction 14 and 21 days postinjury, respectively). Reduced fibrosis in CD36−/− mice was associated with lower levels of profibrotic TH2 cytokines (IL-9, IL-13, IL-4), decreased expression of the M2 macrophage marker Arginase-1, and reduced interstitial myofibroblasts. G2A, on the other hand, was required for optimal clearance of apoptotic neutrophils during zymosan-induced peritoneal inflammation (50.3% increase in apoptotic neutrophils and 30.6% increase in total neutrophils 24 h following zymosan administration in G2A−/− mice). Thus, CD36 is required for timely removal of apoptotic cells in the context of lung injury and modulates subsequent inflammatory and fibrotic processes relevant to fibrotic lung disease. 相似文献
9.
Wójcik M Ramadori P Blaschke M Sultan S Khan S Malik IA Naz N Martius G Ramadori G Schultze FC 《Histochemistry and cell biology》2012,137(2):217-233
It has been suggested that cyclooxygenase-2 (COX-2)-mediated prostaglandin synthesis is associated with liver inflammation
and carcinogenesis. The aim of this study is to identify the cellular source of COX-2 expression in different stages, from
acute liver injury through liver fibrosis to cholangiocarcinoma (CC). We induced in rats acute and “chronic” liver injury
(thioacetamide (TAA) or carbon tetrachloride (CCl4)) and CC development (TAA) and assessed COX-2 gene expression in normal and damaged liver tissue by RT-PCR of total RNA.
The cellular localization of COX-2 protein in liver tissue was analyzed by immunohistochemistry as well as in isolated rat
liver cells by Western blotting. The findings were compared with those obtained in human cirrhotic liver tissue. The specificity
of the antibodies was tested by 2-DE Western blot and mass spectrometric identification of the positive protein spots. RT-PCR
analysis of total RNA revealed an increase of hepatic COX-2 gene expression in acutely as well as “chronically” damaged liver.
COX-2-protein was detected in those ED1+/ED2+ cells located in the non-damaged tissue (resident tissue macrophages). In addition COX-2 positivity in inflammatory mononuclear
phagocytes (ED1+/ED2−), which were also present within the tumoral tissue was detected. COX-2 protein was clearly detectable in isolated Kupffer
cells as well as (at lower level) in isolated “inflammatory” macrophages. Similar results were obtained in human cirrhotic
liver. COX-2 protein is constitutively detectable in liver tissue macrophages. Inflammatory mononuclear phagocytes contribute
to the increase of COX-2 gene expression in acute and chronic liver damage induced by different toxins and in the CC microenvironment. 相似文献
10.
Brigid M. O’Flaherty Caline G. Matar Brian S. Wakeman AnaPatricia Garcia Carol A. Wilke Cynthia L. Courtney Bethany B. Moore Samuel H. Speck 《PloS one》2015,10(8)
Idiopathic pulmonary fibrosis (IPF), one of the most severe interstitial lung diseases, is a progressive fibrotic disorder of unknown etiology. However, there is growing appreciation for the role of viral infection in disease induction and/or progression. A small animal model of multi-organ fibrosis, which involves murine gammaherpesvirus (MHV68) infection of interferon gamma receptor deficient (IFNγR-/-) mice, has been utilized to model the association of gammaherpesvirus infections and lung fibrosis. Notably, several MHV68 mutants which fail to induce fibrosis have been identified. Our current study aimed to better define the role of the unique MHV68 gene, M1, in development of pulmonary fibrosis. We have previously shown that the M1 gene encodes a secreted protein which possesses superantigen-like function to drive the expansion and activation of Vβ4+ CD8+ T cells. Here we show that M1-dependent fibrosis is correlated with heightened levels of inflammation in the lung. We observe an M1-dependent cellular infiltrate of innate immune cells with most striking differences at 28 days-post infection. Furthermore, in the absence of M1 protein expression we observed reduced CD8+ T cells and MHV68 epitope specific CD8+ T cells to the lungs—despite equivalent levels of viral replication between M1 null and wild type MHV68. Notably, backcrossing the IFNγR-/- onto the Balb/c background, which has previously been shown to exhibit weak MHV68-driven Vβ4+ CD8+ T cell expansion, eliminated MHV68-induced fibrosis—further implicating the activated Vβ4+ CD8+ T cell population in the induction of fibrosis. We further addressed the role that CD8+ T cells play in the induction of fibrosis by depleting CD8+ T cells, which protected the mice from fibrotic disease. Taken together these findings are consistent with the hypothesized role of Vβ4+ CD8+ T cells as mediators of fibrotic disease in IFNγR-/- mice. 相似文献
11.
S.J. Le M. Gongora B. Zhang S. Grimmond G.R. Campbell J.H. Campbell B.E. Rolfe 《Differentiation; research in biological diversity》2010,79(4-5):232-243
The cellular response to materials implanted in the peritoneal cavity has been utilised to produce tissue for grafting to hollow smooth muscle organs (blood vessels, bladder, uterus and vas deferens). To gain insight into the regulatory mechanisms involved in encapsulation of a foreign object, and subsequent differentiation of encapsulating cells, the present study used microarray technology and real-time RT-PCR to identify the temporal changes in gene expression associated with tissue development. Immunohistochemical analysis showed that 3–7 days post-implantation of foreign objects (cubes of boiled egg white) into rats, they were encapsulated by tissue comprised primarily of haemopoietic (CD45+) cells, mainly macrophages (CD68+, CCR1+). By day 14, tissue capsule cells no longer expressed CD68, but were positive for myofibroblast markers α-smooth muscle (SM) actin and SM22. In accordance with these results, gene expression data showed that early capsule (days 3–7) development was dominated by the expression of monocyte/macrophage-specific genes (CD14, CSF-1, CSF-1R, MCP-1) and pro-inflammatory mediators such as transforming growth factor (TGF-β). As tissue capsule development progressed (days 14–21), myofibroblast-associated and pro-fibrotic genes (associated with TGF-β and Wnt/β-catenin signalling pathways, including Wnt 4, TGFβRII, connective tissue growth factor (CTGF), SMADs-1, -2, -4 and collagen-1 subunits) were significantly up-regulated. The up-regulation of genes associated with Cardiovascular and Skeletal and Muscular System Development at later time-points suggests the capacity of cells within the tissue capsule for further differentiation to smooth muscle, and possibly other cell types. The identification of key regulatory pathways and molecules associated with the fibrotic response to implanted materials has important applications not only for optimising tissue engineering strategies, but also to control deleterious fibrotic responses. 相似文献
12.
Gregory D. Sempowski Stephen Derdak Richard P. Phipps 《Journal of cellular physiology》1996,167(2):290-296
Pulmonary fibrosis is a potentially fatal consequence of treatments for malignancy and is an increasing problem in bone marrow transplant patients and in cases of allogeneic lung transplant. The fibrotic response is characterized by increases in lung fibroblast number and collagen synthesis. This laboratory previously isolated stable, functionally distinct, murine lung fibroblast subsets (Thy-1+ and Thy-1−) to study the contribution of fibroblast subpopulations in lung fibrosis. The fibroblast fibrotic response may be induced by cytokines secreted by infiltrating cells such as T lymphocytes and mast cells. In the current study two key regulatory cytokines, interferon-γ (IFN-γ) and interleukin-4 (IL-4), were investigated for their effects on the collagen synthesis of murine lung fibroblast subsets. IL-4 and IFN-γ are putatively characterized as fibrogenic and anti-fibrogenic cytokines, respectively, and are found in repairing lung tissue. Stimulation with recombinant IL-4 induced a 100% increase in total collagen production only by Thy-1+ fibroblasts. Types I and III collagen mRNA were increased in the Thy-1+ fibroblasts, unlike the Thy-1− subset. In contrast, IFN-γ decreased constitutive collagen production by more than 50% in Thy-1+ and Thy-1− fibroblasts. Interestingly, the two subsets utilized their collagen production machinery (collagenase, tissue inhibitors of metalloproteinases) differently to further regulate collagen turnover in response to IL-4 and IFN-γ. Overall, our data support the hypothesis that IL-4 is fibrogenic and IFN-γ is anti-fibrogenic. Moreover, selective expansion of IL-4 responsive fibroblasts (e.g., Thy-1+) may be important in the transition from repair to chronic fibrosis. In addition, these data suggest that an inflammatory response dominated by IL-4-producing Th2 lymphocytes and/or mast cells will promote fibrosis development. © 1996 Wiley-Liss, Inc. 相似文献
13.
Guadalupe T. González-Mateo Vanessa Fernández-Míllara Teresa Bellón Georgios Liappas Marta Ruiz-Ortega Manuel López-Cabrera Rafael Selgas Luiz S. Aroeira 《PloS one》2014,9(10)
Fibrosis is a significant health problem associated with a chronic inflammatory reaction. The precise mechanisms involved in the fibrotic process are still poorly understood. However, given that inflammation is a major causative factor, immunomodulation is a possible therapeutic approach to reduce fibrosis. The vitamin D receptor (VDR) that is present in all hematopoietic cells has been associated with immunomodulation. We investigated whether the intraperitoneal administration of paricalcitol, a specific activator of the VDR, modulates peritoneal dialysis fluid (PDF)-induced peritoneal fibrosis. We characterized the inflammatory process in the peritoneal cavity of mice treated or not treated with paricalcitol and analyzed the ensuing fibrosis. The treatment reduced peritoneal IL-17 levels, which strongly correlated with a significantly lower peritoneal fibrotic response. In vitro studies demonstrate that both CD4+ and CD8+ regulatory T cells appear to impact the regulation of IL-17. Paricalcitol treatment resulted in a significantly increased frequency of CD8+ T cells showing a regulatory phenotype. The frequency of CD4+ Tregs tends to be increased, but it did not achieve statistical significance. However, paricalcitol treatment increased the number of CD4+ and CD8+ Treg cells in vivo. In conclusion, the activation of immunological regulatory mechanisms by VDR signaling could prevent or reduce fibrosis, as shown in peritoneal fibrosis induced by PDF exposure in mice. 相似文献
14.
M. Kasper G. Haroske D. Schuh M. Müller R. Koslowski K -W. Wenzel K. Sakai 《Histochemistry and cell biology》1994,102(5):345-352
The colocalization of surfactant protein A (SP-A) and the alveolar macrophage markers ED1 and RM-1, as well as various lectins of the N-acetyl-galactosamine group [Maclura pomifera lectin (MPA), Dolichos biflorus lectin (DBA), soybean agglutinin (SBA)] and of the mannose group [Canavalia ensiformis lectin (ConA), Galanthus nivalis lectin (GNA)] was studied in normal and fibrotic rat lung tissues. In normal tissue, SP-A was located preferentially in the alveolar macrophage subpopulation lacking specific binding sites for lectins of the N-acetylgalactosamine group (DBA and SBA), although 50% of MPA-binding macrophages contained SP-A. The ED1-positive cells were SP-A-negative, whereas SP-A uptake could be detected among the RM-1 immunoreactive as well as the ConA and GNA binding macrophages. In fibrotic lung tissue, however, a small number of .DBA and SBA binding macrophages contained SP-A and the percentage of GNA and ConA binding alveolar macrophages exhibiting SP-A immunoreactivity was reduced. Additionally, the number of ED1+/SP-A+ macrophages was found to be increased. Immunoelectron microscopy revealed accumulation of SP-A in the extracellular space. The differing SP-A content in different alveolar macrophage subpopulations suggests a more complex mechanism of uptake and degradation of surfactant proteins in normal and pathological conditions, which cannot simply be explained by the glycoconjugate pattern on the surface of alveolar macrophages. 相似文献
15.
16.
Typing of hepatic nonparenchymal cells using fibulin-2 and cytoglobin/STAP as liver fibrogenesis-related markers 总被引:2,自引:2,他引:0
Tateaki Y Ogawa T Kawada N Kohashi T Arihiro K Tateno C Obara M Yoshizato K 《Histochemistry and cell biology》2004,122(1):41-49
Fibulin-2 and cytoglobin/stellate cell activation-associated protein (Cygb/STAP) are considered to be markers of hepatic myofibroblasts (MFs) and stellate cells (HSCs), respectively. The aim of the present study was to characterize the nonparenchymal cells (NPCs) of normal rat livers and carbon tetrachloride-induced fibrotic rat livers with respect to the expression of these two proteins. NPCs in normal (Glissons capsules) and fibrotic (fibrotic septa) connective tissues were immunohistochemically categorized into four cell types in terms of the expression of fibulin-2 and Cygb/STAP: fibulin-2 and Cygb/STAP double-positive (Fib+/STAP+); fibulin-2-positive and Cygb/STAP-negative (Fib+/STAP–); Fib–/STAP+; and Fib–/STAP–. The Glissons capsules had Fib+/STAP+ and Fib–/STAP– cell occupancy rates of 45.5% and 54.5%, respectively, but did not contain Fib+/STAP– or Fib–/STAP+ cells. On the other hand, the fibrotic septa contained Fib+/STAP+, Fib–/STAP+, and Fib–/STAP– cells at occupancy rates of 35.0%, 50.5%, and 9.1%, respectively, but did not contain Fib+/STAP– cells. Thus, fibrosis is characterized by a dramatic increase in Fib–/STAP+ NPCs, and a dramatic decrease in Fib–/STAP– NPCs. Fib+/STAP+ NPCs are located uniformly in Glissons capsules and peripherally in fibrotic septa. The present study strongly suggests that Fib+/STAP+ and Fib–/STAP+ NPCs correspond to MFs and activated HSCs, respectively, both of which may contribute to liver fibrogenesis. 相似文献
17.
G-Andre Banat Aleksandra Tretyn Soni Savai Pullamsetti Jochen Wilhelm Andreas Weigert Catherine Olesch Katharina Ebel Thorsten Stiewe Friedrich Grimminger Werner Seeger Ludger Fink Rajkumar Savai 《PloS one》2015,10(9)
Recent studies indicate that the abnormal microenvironment of tumors may play a critical role in carcinogenesis, including lung cancer. We comprehensively assessed the number of stromal cells, especially immune/inflammatory cells, in lung cancer and evaluated their infiltration in cancers of different stages, types and metastatic characteristics potential. Immunohistochemical analysis of lung cancer tissue arrays containing normal and lung cancer sections was performed. This analysis was combined with cyto-/histomorphological assessment and quantification of cells to classify/subclassify tumors accurately and to perform a high throughput analysis of stromal cell composition in different types of lung cancer. In human lung cancer sections we observed a significant elevation/infiltration of total-T lymphocytes (CD3+), cytotoxic-T cells (CD8+), T-helper cells (CD4+), B cells (CD20+), macrophages (CD68+), mast cells (CD117+), mononuclear cells (CD11c+), plasma cells, activated-T cells (MUM1+), B cells, myeloid cells (PD1+) and neutrophilic granulocytes (myeloperoxidase+) compared with healthy donor specimens. We observed all of these immune cell markers in different types of lung cancers including squamous cell carcinoma, adenocarcinoma, adenosquamous cell carcinoma, small cell carcinoma, papillary adenocarcinoma, metastatic adenocarcinoma, and bronchioloalveolar carcinoma. The numbers of all tumor-associated immune cells (except MUM1+ cells) in stage III cancer specimens was significantly greater than those in stage I samples. We observed substantial stage-dependent immune cell infiltration in human lung tumors suggesting that the tumor microenvironment plays a critical role during lung carcinogenesis. Strategies for therapeutic interference with lung cancer microenvironment should consider the complexity of its immune cell composition. 相似文献
18.
Systemic sclerosis (SSc) is an autoimmune connective tissue disease that is characterized by vasculopathy and excessive deposition of extracellular matrix, which causes fibrosis of the skin and internal organs and eventually leads to multiorgan dysfunction. Studies have shown that CD4+ T cell activation is a key factor in the pathogenesis of scleroderma because activated T cells can release various cytokines, resulting in inflammation, microvascular damage and fibrosis. T helper cell 17 (Th17) and regulatory T (Treg) cell activities are a hallmark SSc, as Th17-type cytokines can induce both inflammation and fibrosis. More recently, several studies have reported new T cell subsets, including Th9 and Th22 cells, along with their respective cytokines in the peripheral blood, serum and skin lesions of individuals with SSc. Herein, we review recent data on various CD4+ T helper cell subsets in SSc, and discuss potential roles of these cells in promoting inflammation and fibrosis. 相似文献
19.
Alvaron A. Monteiro Radovan Borojevic 《In vitro cellular & developmental biology. Plant》1987,23(1):10-14
Summary Active fibrous septa are a common feature in liver fibrosis and cirrhosis. Their etiology and formation were studied using
cultures of tissue fragments or cells included in collagen gels. Liver fragments obtained from patients with cirrhosis or
severe schistosomal fibrosis were able to reorganize the gel and to form discrete, interconnecting fibrous septa composed
of parallel arrays of collagen, subsequently colonized by migrating connective tissue cells. The same was obtained in cultures
of fibrogranulomatous lesions isolated from schistosome-infected mice livers. However, fragments of normal human and murine
liver tissue did not show the capacity to form fibrous septa. Septa formation was also obtained in cultures of cell spheroids
formed by liver connective tissue cells isolated from human fibrotic or cirrhotic liver tissues, but not with spheroids of
normal skin fibroblasts or smooth muscle cells.
This experimental model may represent the fibrous septa formation in vivo, depending on the activity of liver connective tissue
cells. The ability of tissue fragments or cell spheroids to form septa in collagen gels might reflect the degree of fibrosis
present in the liver tissue in vivo.
This research was supported by FINEP and CNPq (Brazil) and CNRS (France). 相似文献
20.
Eleni G Tzortzaki Anastassios V Koutsopoulos Konstantina I Dambaki Irini Lambiri Maria Plataki Marion K Gordon Donald R Gerecke Nikolaos M Siafakas 《The journal of histochemistry and cytochemistry》2006,54(6):693-700
Fibril-associated collagens with interrupted triple helices (FACITs) XII and XIV act as fibril organizers and assist in the maintenance of uniform fibril size. We investigated the spatial expression patterns of collagens XII and XIV in cryptogenic organizing pneumonia (COP)/organizing pneumonia (OP) and in idiopathic pulmonary fibrosis (IPF)/usual interstitial pneumonia (UIP) and compared them to normal human lung. Study subjects included 10 patients with COP/OP, 10 patients with IPF/UIP, and 8 control subjects. Immunostaining for collagens XII and XIV was carried out in paraffin-embedded human lung tissue sections. Picrosirius red histochemical staining for collagen I expression and electron microcopy to evaluate fibril diameter were also performed. In normal lung, collagens XII and XIV were expressed in perivascular and subpleural connective tissue. In COP/OP, both collagens showed intense staining in perivascular connective tissue, thickened alveolar septae, and subpleural areas. In IPF/UIP, XII and XIV were expressed in perivascular connective tissue, in areas of established fibrosis, and in areas of subpleural thickening. Only collagen XII was expressed in granulation tissue plugs in COP/OP and in fibroblastic foci in IPF/UIP. Collagen type I was overexpressed in fibrotic areas. Electron micrographs revealed obvious fibril diameter alteration and fusion in the same areas. FACITs XII and XIV are expressed in normal and fibrotic lung. Unlike collagen XIV, collagen XII was expressed in granulation tissue plugs in COP/OP and in fibroblast foci in IPF/UIP. This may suggest a possible distinct role for both collagens in the modulation of the extracellular matrix during the onset of fibrotic process. 相似文献