scholarly journals Stromal “activation” markers do not confer pathogenic activity in tendinopathy

2020 ◽  
Author(s):  
Lindsay A. N. Crowe ◽  
Emma Garcia Melchor ◽  
George A. C. Murrell ◽  
Iain B. McInnes ◽  
Moeed Akbar ◽  
...  
Keyword(s):  
Activation Markers ◽  
Pathogenic Activity ◽  
Stromal Activation

scholarly journals Stromal fibroblast activation and inflammation in frozen shoulder

2018 ◽  
Author(s):  
Moeed Akbar ◽  
Michael McLean ◽  
Emma Garcia-Melchor ◽  
Lindsay AN Crowe ◽  
Paul McMillan ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Immune Cell ◽  
Frozen Shoulder ◽  
Stromal Fibroblast ◽  
Stromal Fibroblasts ◽  
Activation Markers ◽  
Stromal Compartment ◽  
Activation Marker ◽  
Stromal Activation

AbstractIntroductionFrozen shoulder is a common, fibro-proliferative disease characterised by the insidious onset of pain and progressively restricted range of shoulder movement. Despite the prevalence of this disease, there is limited understanding of the molecular mechanisms underpinning the pathogenesis of this debilitating disease. Previous studies have identified increased myofibroblast differentiation and proliferation, immune cell influx and dysregulated cytokine production. We hypothesised that subpopulations within the stromal compartment may take on an activated phenotype, thus initiating the inflammatory processes observed in frozen shoulder. Therefore, we sought to evaluate the presence and possible pathogenic role of known stromal activation proteins in Frozen shoulder,MethodsShoulder capsule samples were collected from 10 patients with idiopathic frozen shoulder and 10 patients undergoing shoulder stabilisation surgery. Stromal activation marker expression (CD248, CD146, VCAM and PDPN, FAP) was quantified using immunohistochemistry. Control and diseased fibroblasts were cultured for in vitro studies from capsule biopsies from instability and frozen shoulder surgeries, respectively. The inflammatory profile and effects of IL-1β upon diseased and control fibroblasts was assessed using ELISA, immunohistochemistry and qPCR.ResultsImmunohistochemistry demonstrated increased expression of stromal activation markers CD248, CD146, VCAM and PDPN in the frozen shoulder group compared with control (p < 0.05). Fibroblasts cultured from diseased capsule produced elevated levels of inflammatory protein (IL-6, IL-8 & CCL-20) in comparison to control fibroblasts. Exposing control fibroblasts to an inflammatory stimuli, (IL-1ß) significantly increased stromal activation marker transcript and protein expression (CD248, PDPN and VCAM).ConclusionsThese results show that stromal fibroblasts have an activated phenotype in frozen shoulder and this is associated with inflammatory cytokine dysregulation. Furthermore, it supports the hypothesis that activated stromal fibroblasts may be involved in regulating the inflammatory and fibrotic processes involved in this disease.

scholarly journals Stromal microenvironment promoted infiltration in esophageal adenocarcinoma and squamous cell carcinoma: a multi-cohort gene-based analysis

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Jiali Li ◽  
Zihang Zeng ◽  
Xueping Jiang ◽  
Nannan Zhang ◽  
Yanping Gao ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Cox Regression ◽  
Macrophage Polarization ◽  
M2 Macrophage ◽  
Activation Markers ◽  
Mesenchymal Transition ◽  
Stromal Microenvironment ◽  
Stromal Activation

Abstract The stromal microenvironment has been shown to affect the infiltration of esophageal carcinoma (ESCA), which is linked to prognosis. However, the complicated mechanism of how infiltration is influenced by the stromal microenvironment is not well-defined. In this study, a stromal activation classifier was established with ridge cox regression to calculate stroma scores for training (n = 182) and validation cohorts (n = 227) based on the stroma-related 32 hub genes identified by sequential bioinformatics algorithms. Patients with high stromal activation were associated with high T stage and poor prognosis in both esophagus adenocarcinoma and esophagus squamous cell carcinoma. Besides, comprehensive multi-omics analysis was used to outline stromal characterizations of 2 distinct stromal groups. Patients with activated tumor stoma showed high stromal cell infiltration (fibroblasts, endothelial cells, and monocyte macrophages), epithelial-mesenchymal transition, tumor angiogenesis and M2 macrophage polarization (CD163 and CD206). Tumor mutation burden of differential stromal groups was also depicted. In addition, a total of 6 stromal activation markers in ESCA were defined and involved in the function of carcinoma-associated fibroblasts that were crucial in the differentiation of distinct stromal characterizations. Based on these studies, a practical classifier for the stromal microenvironment was successfully proposed to predict the prognosis of ESCA patients.

Platelet Surface Activation Markers after DDAVP Infusion in Healthy Subjects

1995 ◽  
Vol 74 (03) ◽  
pp. 991-992 ◽  
Author(s):  
D A Tsakiris ◽  
W E Haefeli ◽  
L Linder ◽  
B Steiner ◽  
G A Marbet
Keyword(s):  
Healthy Subjects ◽  
Surface Activation ◽  
Activation Markers ◽  
Platelet Surface

scholarly journals Early prolonged neutrophil activation in critically ill patients with sepsis

2021 ◽  
Vol 27 (2) ◽  
pp. 192-200
Author(s):  
Sanna Törnblom ◽  
Sara Nisula ◽  
Suvi T Vaara ◽  
Meri Poukkanen ◽  
Sture Andersson ◽  
...  
Keyword(s):  
Intensive Care Unit ◽  
Intensive Care ◽  
Intensive Care Unit Admission ◽  
Plasma Concentrations ◽  
Neutrophil Activation ◽  
Early Event ◽  
Heparin Binding ◽  
Activation Markers ◽  
Heparin Binding Protein ◽  
Pro Inflammatory Cytokines

We hypothesised that plasma concentrations of biomarkers of neutrophil activation and pro-inflammatory cytokines differ according to the phase of rapidly evolving sepsis. In an observational study, we measured heparin-binding protein (HBP), myeloperoxidase (MPO), IL-6 and IL-8 in 167 sepsis patients on intensive care unit admission. We prospectively used the emergence of the first sepsis-associated organ dysfunction (OD) as a surrogate for the sepsis phase. Fifty-five patients (of 167, 33%) developed the first OD > 1 h before, 74 (44%) within ± 1 h, and 38 (23%) > 1 h after intensive care unit admission. HBP and MPO were elevated at a median of 12 h before the first OD, remained high up to 24 h, and were not associated with sepsis phase. IL-6 and IL-8 rose and declined rapidly close to OD emergence. Elevation of neutrophil activation markers HBP and MPO was an early event in the evolution of sepsis, lasting beyond the subsidence of the pro-inflammatory cytokine reaction. Thus, as sepsis biomarkers, HBP and MPO were not as prone as IL-6 and IL-8 to the effect of sample timing.

scholarly journals Targeting Toll-Like Receptor 2: Polarization of Porcine Macrophages by a Mycoplasma-Derived Pam2cys Lipopeptide

Vaccines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 692
Author(s):  
Giulia Franzoni ◽  
Antonio Anfossi ◽  
Chiara Grazia De Ciucis ◽  
Samanta Mecocci ◽  
Tania Carta ◽  
...  
Keyword(s):  
Mhc Class Ii ◽  
Macrophage Polarization ◽  
Surface Protein ◽  
Antimicrobial Activities ◽  
Toll Like Receptor ◽  
Activation Markers ◽  
Class I Mhc ◽  
Toll Like Receptor 2

Toll-like receptor 2 (TLR2) ligands are attracting increasing attention as prophylactic and immunotherapeutic agents against pathogens and tumors. We previously observed that a synthetic diacylated lipopeptide based on a surface protein of Mycoplasma agalactiae (Mag-Pam2Cys) strongly activated innate immune cells, including porcine monocyte-derived macrophages (moMΦ). In this study, we utilized confocal microscopy, flow cytometry, multiplex cytokine ELISA, and RT-qPCR to conduct a comprehensive analysis of the effects of scalar doses of Mag-Pam2Cys on porcine moMΦ. We observed enhanced expression of activation markers (MHC class I, MHC class II DR, CD25), increased phagocytotic activity, and release of IL-12 and proinflammatory cytokines. Mag-Pam2Cys also upregulated the gene expression of several IFN-α subtypes, p65, NOS2, and molecules with antimicrobial activities (CD14, beta defensin 1). Overall, our data showed that Mag-Pam2Cys polarized porcine macrophages towards a proinflammatory antimicrobial phenotype. However, Mag-Pam2Cys downregulated the expression of IFN-α3, six TLRs (TLR3, -4, -5, -7, -8, -9), and did not interfere with macrophage polarization induced by the immunosuppressive IL-10, suggesting that the inflammatory activity evoked by Mag-Pam2Cys could be regulated to avoid potentially harmful consequences. We hope that our in vitro results will lay the foundation for the further evaluation of this diacylated lipopeptide as an immunopotentiator in vivo.

scholarly journals Placental Complement Activation in Fetal and Neonatal Alloimmune Thrombocytopenia: An Observational Study

2021 ◽  
Vol 22 (13) ◽  
pp. 6763
Author(s):  
Thijs W. de Vos ◽  
Dian Winkelhorst ◽  
Hans J. Baelde ◽  
Kyra L. Dijkstra ◽  
Rianne D. M. van Bergen ◽  
...  
Keyword(s):  
Complement Activation ◽  
Histopathological Examination ◽  
Hla Class I ◽  
Unknown Etiology ◽  
Low Grade ◽  
Classical Pathway ◽  
Newly Diagnosed ◽  
Activation Markers ◽  
Amsterdam Criteria ◽  
Alloimmune Thrombocytopenia

Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a disease that causes thrombocytopenia and a risk of bleeding in the (unborn) child that result from maternal alloantibodies directed against fetal, paternally inherited, human platelet antigens (HPA). It is hypothesized that these alloantibodies can also bind to the placenta, causing placental damage. This study aims to explore signs of antibody-mediated placental damage in FNAIT. We performed a retrospective study that included pregnant women, their newborns, and placentas. It comprised 23 FNAIT cases, of which nine were newly diagnosed (14 samples) and 14 were antenatally treated with intravenous immune globulins (IVIg) (21 samples), and 20 controls, of which 10 had anti-HLA-class I antibodies. Clinical information was collected from medical records. Placental samples were stained for complement activation markers (C1q, C4d, SC5b-9, and mannose-binding lectin) using immunohistochemistry. Histopathology was examined according to the Amsterdam criteria. A higher degree of C4d deposition was present in the newly diagnosed FNAIT cases (10/14 samples), as compared to the IVIg-treated FNAIT cases (2/21 samples, p = 0.002) and anti-HLA-negative controls (3/20 samples, p = 0.006). A histopathological examination showed delayed maturation in four (44%) placentas in the newly diagnosed FNAIT cases, five (36%) in the IVIg-treated FNAIT cases, and one in the controls (NS). C4d deposition at the syncytiotrophoblast was present in combination with low-grade villitis of unknown etiology in three newly diagnosed FNAIT cases that were born SGA. We conclude that a higher degree of classical pathway-induced complement activation is present in placentas from pregnancies with untreated FNAIT. This may affect placental function and fetal growth.

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