scholarly journals CX3CR1–fractalkine axis drives kinetic changes of monocytes in fibrotic interstitial lung diseases

2019 ◽  
Vol 55 (2) ◽  
pp. 1900460
Author(s):  
Flavia R. Greiffo ◽  
Valeria Viteri-Alvarez ◽  
Marion Frankenberger ◽  
Daniela Dietel ◽  
Almudena Ortega-Gomez ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Lung Diseases ◽  
Hypersensitivity Pneumonitis ◽  
Immune Cell ◽  
Interstitial Lung Diseases ◽  
Flow Cytometry Analysis ◽  
Bronchial Epithelial ◽  
Fibrotic Process ◽  
Nonspecific Interstitial Pneumonia ◽  
Classical Monocytes

Circulating immune cell populations have been shown to contribute to interstitial lung disease (ILD). In this study, we analysed circulating and lung resident monocyte populations, and assessed their phenotype and recruitment from the blood to the lung in ILD. Flow cytometry analysis of blood samples for quantifying circulating monocytes was performed in 105 subjects: 83 with ILD (n=36, n=28 and n=19 for nonspecific interstitial pneumonia, hypersensitivity pneumonitis and connective-tissue disease-associated ILD, respectively), as well as 22 controls. Monocyte localisation and abundance were assessed using immunofluorescence and flow cytometry of lung tissue. Monocyte populations were cultured either alone or with endothelial cells to assess fractalkine-dependent transmigration pattern. We show that circulating classical monocytes (CM) were increased in ILD compared with controls, while nonclassical monocytes (NCM) were decreased. CM abundance correlated inversely with lung function, while NCM abundance correlated positively. Both CCL2 and CX3CL1 concentrations were increased in plasma and lungs of ILD patients. Fractalkine co-localised with ciliated bronchial epithelial cells, thereby creating a chemoattractant gradient towards the lung. Fractalkine enhanced endothelial transmigration of NCM in ILD samples only. Immunofluorescence, as well as flow cytometry, showed an increased presence of NCM in fibrotic niches in ILD lungs. Moreover, NCM in the ILD lungs expressed increased CX3CR1, M2-like and phagocytic markers. Taken together, our data support that in ILD, fractalkine drives the migration of CX3CR1+ NCM to the lungs, thereby perpetuating the local fibrotic process.

scholarly journals Presentation, diagnosis and clinical course of the spectrum of progressive-fibrosing interstitial lung diseases

2018 ◽  
Vol 27 (150) ◽  
pp. 180076 ◽  
Author(s):  
Vincent Cottin ◽  
Nikhil A. Hirani ◽  
David L. Hotchkin ◽  
Anoop M. Nambiar ◽  
Takashi Ogura ◽  
...  
Keyword(s):  
Interstitial Pneumonia ◽  
Lung Diseases ◽  
Hypersensitivity Pneumonitis ◽  
Early Death ◽  
Occupational Exposures ◽  
Interstitial Lung Diseases ◽  
Lung Function Decline ◽  
Nonspecific Interstitial Pneumonia ◽  
Immunomodulatory Therapies

Although these conditions are rare, a proportion of patients with interstitial lung diseases (ILDs) may develop a progressive-fibrosing phenotype. Progressive fibrosis is associated with worsening respiratory symptoms, lung function decline, limited response to immunomodulatory therapies, decreased quality of life and, potentially, early death. Idiopathic pulmonary fibrosis may be regarded as a model for other progressive-fibrosing ILDs. Here we focus on other ILDs that may present a progressive-fibrosing phenotype, namely idiopathic nonspecific interstitial pneumonia, unclassifiable idiopathic interstitial pneumonia, connective tissue disease-associated ILDs (e.g.rheumatoid arthritis-related ILD), fibrotic chronic hypersensitivity pneumonitis, fibrotic chronic sarcoidosis and ILDs related to other occupational exposures. Differential diagnosis of these ILDs can be challenging, and requires detailed consideration of clinical, radiological and histopathological features. Accurate and early diagnosis is crucial to ensure that patients are treated optimally.

O40-1 Risk of hypersensitivity pneumonitis and other interstitial lung diseases among pigeon breeders

2016 ◽  
Author(s):  
Christine Cramer ◽  
Vivi Schlünssen ◽  
Elisabeth Bendstrup ◽  
Zara Ann Stokholm ◽  
Jesper Medom Vestergaard ◽  
...  
Keyword(s):  
Lung Diseases ◽  
Hypersensitivity Pneumonitis ◽  
Interstitial Lung Diseases

scholarly journals Pharmacological management of progressive-fibrosing interstitial lung diseases: a review of the current evidence

2018 ◽  
Vol 27 (150) ◽  
pp. 180074 ◽  
Author(s):  
Luca Richeldi ◽  
Francesco Varone ◽  
Miguel Bergna ◽  
Joao de Andrade ◽  
Jeremy Falk ◽  
...  
Keyword(s):  
Interstitial Pneumonia ◽  
Lung Diseases ◽  
Occupational Exposures ◽  
Interstitial Lung Diseases ◽  
Therapeutic Options ◽  
Current Evidence ◽  
Pharmacological Management ◽  
The Status ◽  
Nonspecific Interstitial Pneumonia ◽  
Randomised Controlled

A proportion of patients with interstitial lung diseases (ILDs) are at risk of developing a progressive-fibrosing phenotype, which is associated with a deterioration in lung function and early mortality. In addition to idiopathic pulmonary fibrosis (IPF), fibrosing ILDs that may present a progressive phenotype include idiopathic nonspecific interstitial pneumonia, connective tissue disease-associated ILDs, hypersensitivity pneumonitis, unclassifiable idiopathic interstitial pneumonia, ILDs related to other occupational exposures and sarcoidosis. Corticosteroids and/or immunosuppressive therapies are sometimes prescribed to patients with these diseases. However, this treatment regimen may not be effective, adequate on its own or well tolerated, suggesting that there is a pressing need for efficacious and better tolerated therapies. Currently, the only approved treatments to slow disease progression in patients with IPF are nintedanib and pirfenidone. Similarities in pathobiological mechanisms leading to fibrosis between IPF and other ILDs that may present a progressive-fibrosing phenotype provide a rationale to suggest that nintedanib and pirfenidone may be therapeutic options for patients with the latter diseases.This review provides an overview of the therapeutic options currently available for patients with fibrosing ILDs, including fibrosing ILDs that may present a progressive phenotype, and explores the status of the randomised controlled trials that are underway to determine the efficacy and safety of nintedanib and pirfenidone.

scholarly journals Morphomolecular motifs of pulmonary neoangiogenesis in interstitial lung diseases

2019 ◽  
Vol 55 (3) ◽  
pp. 1900933 ◽  
Author(s):  
Maximilian Ackermann ◽  
Helge Stark ◽  
Lavinia Neubert ◽  
Stephanie Schubert ◽  
Paul Borchert ◽  
...  
Keyword(s):  
Gene Expression ◽  
Blood Vessels ◽  
Expression Analysis ◽  
Lung Diseases ◽  
Gene Expression Analysis ◽  
Interstitial Lung Diseases ◽  
Corrosion Casting ◽  
Cellular Functions ◽  
Microvascular Architecture ◽  
Nonspecific Interstitial Pneumonia

The pathogenetic role of angiogenesis in interstitial lung diseases (ILDs) is controversial. This study represents the first investigation of the spatial complexity and molecular motifs of microvascular architecture in important subsets of human ILD. The aim of our study was to identify specific variants of neoangiogenesis in three common pulmonary injury patterns in human ILD.We performed comprehensive and compartment-specific analysis of 24 human lung explants with usual intersitial pneumonia (UIP), nonspecific interstitial pneumonia (NSIP) and alveolar fibroelastosis (AFE) using histopathology, microvascular corrosion casting, micro-comupted tomography based volumetry and gene expression analysis using Nanostring as well as immunohistochemistry to assess remodelling-associated angiogenesis.Morphometrical assessment of vessel diameters and intervascular distances showed significant differences in neoangiogenesis in characteristically remodelled areas of UIP, NSIP and AFE lungs. Likewise, gene expression analysis revealed distinct and specific angiogenic profiles in UIP, NSIP and AFE lungs.Whereas UIP lungs showed a higher density of upstream vascularity and lower density in perifocal blood vessels, NSIP and AFE lungs revealed densely packed alveolar septal blood vessels. Vascular remodelling in NSIP and AFE is characterised by a prominent intussusceptive neoangiogenesis, in contrast to UIP, in which sprouting of new vessels into the fibrotic areas is characteristic. The molecular analyses of the gene expression provide a foundation for understanding these fundamental differences between AFE and UIP and give insight into the cellular functions involved.

scholarly journals Occupational Extrinsic Allergic Alveolitis in a poultry farmer

2020 ◽  
Vol 71 (1) ◽  
pp. 69-73
Author(s):  
Smărăndescu Raluca Andreea ◽  
Mircea-Constantin Diaconu ◽  
Claudia-Mariana Handra ◽  
Agripina Rașcu
Keyword(s):  
Lung Diseases ◽  
Hypersensitivity Pneumonitis ◽  
Chemical Compounds ◽  
Interstitial Lung Diseases ◽  
Risk Exposure ◽  
Low Molecular Weight ◽  
Organic Substances ◽  
Extrinsic Allergic Alveolitis ◽  
Allergic Alveolitis ◽  
The One

AbstractHypersensitivity pneumonitis is a group of inflammatory interstitial lung diseases caused by hypersensitivity immune reactions to the inhalation of various antigens: fungal, bacterial, animal protein, or chemical sources, finely dispersed, with aerodynamic diameter <5μ, representing the respirable fraction. The national register for interstitial lung diseases records very few cases of hypersensitivity pneumonitis (extrinsec allergic alveolitis), a well defined occupational disease. Although not an eminently of occupational origin, the extrinsec allergic alveolitis can occur secondary to occupational exposure to organic substances (animal or insect proteins, bacteria, fungi) or inorganic (low molecular weight chemical compounds) and the occupational doctor is a key actor in the diagnosys. The disease has chronic evolution and exposure avoidance, as early as possible, has major prognostic influence. The occupational anamnesis remains the most important step and the occupational physician is the one in charge for monitoring and detection of the presence of respiratory symptoms in all employees with risk exposure. Next, we present the case of a farmer, without other comorbidities, who develops various respiratory and systemic diseases and manifestations due to repeated exposure to animal proteins and molds, in order to review the risk factors and the consequences of exposure in poultry farms.

scholarly journals Update in Diagnosis and Management of Interstitial Lung Diseases

2021 ◽  
Vol 9 (7) ◽  
Author(s):  
Mauricio Salinas ◽  
Matias Florenzano
Keyword(s):  
Lung Diseases ◽  
Hypersensitivity Pneumonitis ◽  
Connective Tissue Diseases ◽  
Interstitial Lung Diseases ◽  
Diverse Group ◽  
Principal Characteristics ◽  
Diagnosis And Management ◽  
New Concepts ◽  
Lung Abnormalities ◽  
Diagnosis Approach

Interstitial lung diseases (ILD) are a complex and diverse group of disorders. ILD are more frequently diagnosed and prevalent now. In this article, diagnosis approach, including new bronchoscopy and genetic tools, and some recently added concepts are revisited, as progressive fibrosing interstitial lung diseases and interstitial lung abnormalities. Recently information relative to idiopathic pulmonary fibrosis is shown, including genetics and pathophysiology. We look over the dynamic world of interstitial lung diseases related to connective tissue diseases, principal characteristics of this group and the principles that define which of the various available therapies should be chosen. Finally new concepts and guidelines published about the diagnosis and management of hypersensitivity pneumonitis are reported. New data and treatments have changed our traditional vision of these lung diseases and we will new options in the next years.

Humanized mice (humice) carrying patient-derived xenograft (PDX) as a platform to develop immunotherapy in bladder cancer (BCa).

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 381-381 ◽  
Author(s):  
Chong-xian Pan ◽  
Wei Shi ◽  
Ai-Hong Ma ◽  
Hongyong Zhang ◽  
Primo Lara ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Tumor Growth ◽  
Immune Cell ◽  
Tumor Regression ◽  
Genetic Alterations ◽  
Therapeutic Modality ◽  
Whole Body ◽  
Flow Cytometry Analysis ◽  
Nsg Mice ◽  
Human Immune

381 Background: Immunotherapy with anti-programmed cell death 1 (PD1) or PD ligand 1 (PD-L1) antibody has emerged as a promising therapeutic modality, but has a response rate of approximately 20% in BCa. There are various drawbacks associated with current animal models. The objective of this study is to establish and characterize humice carrying PDXs in which both the immune cells and BCa cells are derived from humans. Methods: NOD-scid IL2Rgammanull or NSG, mice received CD34+ hematopoietic progenitor cells (HPC) cells i.v. after whole body radiation. PDXs were established through direct implantation of human BCa clinical specimens into NSG mice. Immune cell subpopulations were analyzed through flow cytometry analysis. Humice carrying HLA-unmatched PDXs were treated with an anti-PD1 antibody pemborlizumab (pembro) or in combination with a BKT/ITK inhibitor ibrutinib to determine the anti-tumor efficacy and toxicity. Results: PDXs retained the morphology fidelity and 92-97% of genetic alterations of parental patient cancers. Of the first 8 PDXs tested, 3 had high PD-L1 ( > 10 FPKM) as determined by RNA-seq which was further confirmed with flow cytometry analysis. Major human immune cell sub-populations were reconstituted in humice. No xenograft versus host disease was observed before pembro treatment. In humice with HPC donor 6466, pembro significantly inhibited tumor growth (p = 0.0016 at Day 29) of PDX BL293, but had no effect in another PDX BL440 with the same HPC donor 6466, or with the same PDX BL293 but with a different HPC donor 912. In another set of humice (HPC donor 710) carrying PDX BL293, pembro alone inhibited tumor growth. However, addition of ibrutinib did not potentiate the efficacy of pembro, but increased toxicity. Tumor regression with pembro treatment was associated with decrease of CD4+PD1+, CD8+PD1+ cells at peripheral blood and increased CD45+ and CD8+ cells in PDXs. Conclusions: Humice carrying PDXs reconstitute with human immune system, and can potentially be used to screen for effective immunotherapeutic agents or combinations, and to study resistant mechanisms.

scholarly journals Radiological diagnosis of interstitial lung diseases

2013 ◽  
Vol 66 (suppl. 1) ◽  
pp. 29-33
Author(s):  
Ruza Stevic ◽  
Vucinic Mihailovic ◽  
Dragana Jovanovic ◽  
Nada Vasic
Keyword(s):  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Interstitial Pneumonia ◽  
Lung Diseases ◽  
Usual Interstitial Pneumonia ◽  
Interstitial Lung Diseases ◽  
Ground Glass ◽  
Cryptogenic Organizing Pneumonia ◽  
Acute Interstitial Pneumonia ◽  
Nonspecific Interstitial Pneumonia

Introduction. Interstitial lung diseases include the entities of idiopathic pulmonary fibrosis, nonspecific interstitial pneumonia, cryptogenic organizing pneumonia, acute interstitial pneumonia, respiratory bronchiolitis-associated interstitial lung disease, desquamative interstitial pneumonia, and lymphocytic interstitial pneumonia. Recent introduction of high-resolution computed tomography has made the diagnosis of interstitial lung disease much easier. Usual interstitial pneumonia A predominantly subpleural reticulation and honeycombing at the basal posterior part of the lung with a progression to anterior and superior parts are characteristic of usual interstitial pneumonia/ idiopathic pulmonary fibrosis. Nonspecific interstitial pneumonia Typical findings of nonspecific interstitial pneumonia are bilateral, relatively symmetrical subpleural ground glass opacifications and irregular linear opacities. Desquamative interstitial pneumonia is characterized by diffuse symmetrical ground glass opacifications. Respiratory bronchiolitisassociated interstitial lung disease Centrilobular nodules and irregular ground glass opacifications are present. Cryptogenic organizing pneumonia Subpleural and peribronchial consolidations are prominent findings that are not present in other idiopathic interstitial pneumonias. Acute interstitial pneumonia. Bilateral ground-glass opacifications are present and areas of peripheral consolidations may also be seen in acute interstitial pneumonia. Lymphocytic interstitial pneumonia. Diffuse or patchy areas of ground glass opacification with centrilobular nodules and occasionally well-defined cysts are seen. Conclusion. Imaging plays a crucial role in identifying interstitial lung diseases but precise diagnosis requires a dynamic interdisciplinary approach that correlates clinical, radiological and pathologic features.

Sign in / Sign up

Export Citation Format

Share Document