Depletion of pulmonary intravascular macrophages inhibits acute lung inflammation

2004 ◽  
Vol 286 (2) ◽  
pp. L363-L372 ◽  
Author(s):  
Baljit Singh ◽  
Jacqueline W. Pearce ◽  
Lakshman N. Gamage ◽  
Kyathanahalli Janardhan ◽  
Sarah Caldwell
Keyword(s):  
Lung Inflammation ◽  
Acute Inflammation ◽  
Inflammatory Cells ◽  
Acute Lung Inflammation ◽  
Tnf Α ◽  
Highly Sensitive ◽  
In Vitro Exposure ◽  
Pulmonary Intravascular Macrophages

Pulmonary intravascular macrophages (PIMs) are present in ruminants and horses. These species are highly sensitive to acute lung inflammation compared with non-PIM-containing species such as rats and humans. There is evidence that rats and humans may also recruit PIMs under certain conditions. We investigated precise contributions of PIMs to acute lung inflammation in a calf model. First, PIMs were recognized with a combination of in vivo phagocytic tracer Monastral blue and postembedding immunohistology with anti-CD68 monoclonal antibody. Second, gadolinium chloride depleted PIMs within 48 h of treatment ( P < 0.05). Finally, PIMs contain TNF-α, and their depletion reduces cells positive for IL-8 ( P < 0.05) and TNF-α ( P < 0.05) and histopathological signs of acute lung inflammation in calves infected with Mannheimia hemolytica. The majority of IL-8-positive inflammatory cells in lung septa of infected calves were platelets. Platelets from normal cattle contained preformed IL-8 that was released upon in vitro exposure to thrombin ( P < 0.05). These novel data show that PIMs, as the source of TNF-α, promote recruitment of inflammatory cells including IL-8-containing platelets to stimulate acute inflammation and pathology in lungs. These data may also be relevant to humans due to our ability to recruit PIMs.

scholarly journals Combined In Vitro and In Vivo Approaches to Propose a Putative Adverse Outcome Pathway for Acute Lung Inflammation Induced by Nanoparticles: A Study on Carbon Dots

Nanomaterials ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 180
Author(s):  
Maud Weiss ◽  
Jiahui Fan ◽  
Mickaël Claudel ◽  
Luc Lebeau ◽  
Françoise Pons ◽  
...  
Keyword(s):  
Carbon Dots ◽  
Lung Inflammation ◽  
Adverse Outcome ◽  
Cellular Responses ◽  
Target Cells ◽  
Inflammasome Activation ◽  
Adverse Outcome Pathway ◽  
Acute Lung Inflammation

With the growth of nanotechnologies, concerns raised regarding the potential adverse effects of nanoparticles (NPs), especially on the respiratory tract. Adverse outcome pathways (AOP) have become recently the subject of intensive studies in order to get a better understanding of the mechanisms of NP toxicity, and hence hopefully predict the health risks associated with NP exposure. Herein, we propose a putative AOP for the lung toxicity of NPs using emerging nanomaterials called carbon dots (CDs), and in vivo and in vitro experimental approaches. We first investigated the effect of a single administration of CDs on mouse airways. We showed that CDs induce an acute lung inflammation and identified airway macrophages as target cells of CDs. Then, we studied the cellular responses induced by CDs in an in vitro model of macrophages. We observed that CDs are internalized by these cells (molecular initial event) and induce a series of key events, including loss of lysosomal integrity and mitochondrial disruption (organelle responses), as well as oxidative stress, inflammasome activation, inflammatory cytokine upregulation and macrophage death (cellular responses). All these effects triggering lung inflammation as tissular response may lead to acute lung injury.

scholarly journals The Crucial Role of PPARγ-Egr-1-Pro-Inflammatory Mediators Axis in IgG Immune Complex-Induced Acute Lung Injury

2021 ◽  
Vol 12 ◽  
Author(s):  
Chunguang Yan ◽  
Jing Chen ◽  
Yue Ding ◽  
Zetian Zhou ◽  
Bingyu Li ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Immune Complex ◽  
Inflammatory Mediators ◽  
Lung Inflammation ◽  
Acute Lung Inflammation ◽  
Pparγ Agonist

BackgroundThe ligand-activated transcription factor peroxisome proliferator-activated receptor (PPAR) γ plays crucial roles in diverse biological processes including cellular metabolism, differentiation, development, and immune response. However, during IgG immune complex (IgG-IC)-induced acute lung inflammation, its expression and function in the pulmonary tissue remains unknown.ObjectivesThe study is designed to determine the effect of PPARγ on IgG-IC-triggered acute lung inflammation, and the underlying mechanisms, which might provide theoretical basis for therapy of acute lung inflammation.SettingDepartment of Pathogenic Biology and Immunology, Medical School of Southeast UniversitySubjectsMice with down-regulated/up-regulated PPARγ activity or down-regulation of Early growth response protein 1 (Egr-1) expression, and the corresponding controls.InterventionsAcute lung inflammation is induced in the mice by airway deposition of IgG-IC. Activation of PPARγ is achieved by using its agonist Rosiglitazone or adenoviral vectors that could mediate overexpression of PPARγ. PPARγ activity is suppressed by application of its antagonist GW9662 or shRNA. Egr-1 expression is down-regulated by using the gene specific shRNA.Measures and Main ResultsWe find that during IgG-IC-induced acute lung inflammation, PPARγ expression at both RNA and protein levels is repressed, which is consistent with the results obtained from macrophages treated with IgG-IC. Furthermore, both in vivo and in vitro data show that PPARγ activation reduces IgG-IC-mediated pro-inflammatory mediators’ production, thereby alleviating lung injury. In terms of mechanism, we observe that the generation of Egr-1 elicited by IgG-IC is inhibited by PPARγ. As an important transcription factor, Egr-1 transcription is substantially increased by IgG-IC in both in vivo and in vitro studies, leading to augmented protein expression, thus amplifying IgG-IC-triggered expressions of inflammatory factors via association with their promoters.ConclusionDuring IgG-IC-stimulated acute lung inflammation, PPARγ activation can relieve the inflammatory response by suppressing the expression of its downstream target Egr-1 that directly binds to the promoter regions of several inflammation-associated genes. Therefore, regulation of PPARγ-Egr-1-pro-inflammatory mediators axis by PPARγ agonist Rosiglitazone may represent a novel strategy for blockade of acute lung injury.

Role of surface complexed iron in oxidant generation and lung inflammation induced by silicates

1992 ◽  
Vol 263 (5) ◽  
pp. L511-L518 ◽  
Author(s):  
A. J. Ghio ◽  
T. P. Kennedy ◽  
A. R. Whorton ◽  
A. L. Crumbliss ◽  
G. E. Hatch ◽  
...  
Keyword(s):  
Respiratory Burst ◽  
Lung Inflammation ◽  
Important Determinant ◽  
Surface Complexation ◽  
Oxidative Degradation ◽  
Transition Metal Ions ◽  
Leukotriene B4 ◽  
Acute Lung Inflammation

Inhalation of silicates induces a variety of lung diseases in humans. The molecular mechanism(s) by which these dusts cause disease is not known. Because several naturally occurring mineral oxides have large amounts of transition metal ions on their surfaces, we tested the hypothesis that surface complexation of iron may be an important determinant of their ability to induce disease. Silica, crocidolite, kaolinite, and talc complexed considerable concentrations of Fe3+ onto their surfaces from both in vitro and in vivo sources. The potential biological importance of iron complexation was assessed by examining the relationship between surface [Fe3+] and the ability of silicates to mediate oxidative degradation of deoxyribose in vitro, induce a respiratory burst and elicit leukotriene B4 (LTB4) release by alveolar macrophages (AM) in vitro, and cause acute alveolitis after intratracheal insufflation. For these studies, three varieties of silicate dusts were used: iron-loaded, wetted (unmodified), and deferoxamine-treated to remove Fe3+. The ability of silicates to catalyze oxidant generation in an ascorbate/H2O2 system in vitro, to trigger respiratory burst activity and LTB4 release by AM, and to induce acute lung inflammation in the rat all increased with surface complexed Fe3+. The results of these studies suggest that surface complexation of iron may be an important determinant in the pathogenesis of disease after silicate exposure.

Ultrastructural study of uptake of monastral blue by the pulmonary intravascular macrophages of sheep in the presence and absence of surface coat

1992 ◽  
Vol 50 (1) ◽  
pp. 702-703
Author(s):  
B. Singh ◽  
D. S. Jassal ◽  
O. S. Atwal ◽  
K. Minhas
Keyword(s):  
Tannic Acid ◽  
Animal Species ◽  
Ultrastructural Level ◽  
Mononuclear Phagocyte ◽  
Surface Coat ◽  
Cell Periphery ◽  
Highly Sensitive ◽  
Pulmonary Intravascular Macrophages

Pulmonary intravascular macrophage (PIM) is an important mononuclear phagocyte of some animal species. In sheep these cells are actively involved in the clearance of microbes and endotoxins. By treating the tissue with tannic acid we have identified at the ultrastructural level a unique globular surface coat, arranged at a distance of 30-40 nm from the cell periphery, This coat is hypothesized to be lipoprotein in nature as tannic acid complexes with the globules to enhance their electron density. This surface coat is highly sensitive to in vitro lipolytic lipase digestion and in vivo heparin treatment.

scholarly journals Regulation of eosinophilia and allergic airway inflammation by the glycan-binding protein galectin-1

2016 ◽  
Vol 113 (33) ◽  
pp. E4837-E4846 ◽  
Author(s):  
Xiao Na Ge ◽  
Sung Gil Ha ◽  
Yana G. Greenberg ◽  
Amrita Rao ◽  
Idil Bastan ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Binding Protein ◽  
Allergic Airway Inflammation ◽  
Inflammatory Cells ◽  
Cell Clustering ◽  
Tnf Α ◽  
Chemokine Receptor Ccr3 ◽  
Cell Adhesion Molecule 1

Galectin-1 (Gal-1), a glycan-binding protein with broad antiinflammatory activities, functions as a proresolving mediator in autoimmune and chronic inflammatory disorders. However, its role in allergic airway inflammation has not yet been elucidated. We evaluated the effects of Gal-1 on eosinophil function and its role in a mouse model of allergic asthma. Allergen exposure resulted in airway recruitment of Gal-1–expressing inflammatory cells, including eosinophils, as well as increased Gal-1 in extracellular spaces in the lungs. In vitro, extracellular Gal-1 exerted divergent effects on eosinophils that were N-glycan– and dose-dependent. At concentrations ≤0.25 µM, Gal-1 increased eosinophil adhesion to vascular cell adhesion molecule-1, caused redistribution of integrin CD49d to the periphery and cell clustering, but inhibited ERK(1/2) activation and eotaxin-1–induced migration. Exposure to concentrations ≥1 µM resulted in ERK(1/2)-dependent apoptosis and disruption of the F-actin cytoskeleton. At lower concentrations, Gal-1 did not alter expression of adhesion molecules (CD49d, CD18, CD11a, CD11b, L-selectin) or of the chemokine receptor CCR3, but decreased CD49d and CCR3 was observed in eosinophils treated with higher concentrations of this lectin. In vivo, allergen-challenged Gal-1–deficient mice exhibited increased recruitment of eosinophils and CD3+ T lymphocytes in the airways as well as elevated peripheral blood and bone marrow eosinophils relative to corresponding WT mice. Further, these mice had an increased propensity to develop airway hyperresponsiveness and displayed significantly elevated levels of TNF-α in lung tissue. This study suggests that Gal-1 can limit eosinophil recruitment to allergic airways and suppresses airway inflammation by inhibiting cell migration and promoting eosinophil apoptosis.

scholarly journals Could Arachidonic Acid-Derived Pro-Resolving Mediators Be a New Therapeutic Strategy for Asthma Therapy?

2020 ◽  
Vol 11 ◽  
Author(s):  
Daniella Bianchi Reis Insuela ◽  
Maximiliano Ruben Ferrero ◽  
Diego de Sá Coutinho ◽  
Marco Aurélio Martins ◽  
Vinicius Frias Carvalho
Keyword(s):  
Arachidonic Acid ◽  
Inflammatory Response ◽  
Lung Inflammation ◽  
Clinical Investigation ◽  
Inflammatory Cells ◽  
Airway Epithelial ◽  
Asthmatic Patients ◽  
Beneficial Effects

Asthma represents one of the leading chronic diseases worldwide and causes a high global burden of death and disability. In asthmatic patients, the exacerbation and chronification of the inflammatory response are often related to a failure in the resolution phase of inflammation. We reviewed the role of the main arachidonic acid (AA) specialized pro-resolving mediators (SPMs) in the resolution of chronic lung inflammation of asthmatics. AA is metabolized by two classes of enzymes, cyclooxygenases (COX), which produce prostaglandins (PGs) and thromboxanes, and lypoxygenases (LOX), which form leukotrienes and lipoxins (LXs). In asthma, two primary pro-resolving derived mediators from COXs are PGE2 and the cyclopentenone prostaglandin15-Deoxy-Delta-12,14-PGJ2 (15d-PGJ2) while from LOXs are the LXA4 and LXB4. In different models of asthma, PGE2, 15d-PGJ2, and LXs reduced lung inflammation and remodeling. Furthermore, these SPMs inhibited chemotaxis and function of several inflammatory cells involved in asthma pathogenesis, such as eosinophils, and presented an antiremodeling effect in airway epithelial, smooth muscle cells and fibroblasts in vitro. In addition, PGE2, 15d-PGJ2, and LXs are all able to induce macrophage reprogramming to an alternative M2 pro-resolving phenotype in vitro and in vivo. Although PGE2 and LXA4 showed some beneficial effects in asthmatic patients, there are limitations to their clinical use, since PGE2 caused side effects, while LXA4 presented low stability. Therefore, despite the strong evidence that these AA-derived SPMs induce resolution of both inflammatory response and tissue remodeling in asthma, safer and more stable analogs must be developed for further clinical investigation of their application in asthma treatment.

Two indole-2-carboxamide derivatives attenuate lipopolysaccharide-induced acute lung injury by inhibiting inflammatory response

2018 ◽  
Vol 96 (12) ◽  
pp. 1261-1267
Author(s):  
Wei Dai ◽  
Xiangting Ge ◽  
Tingting Xu ◽  
Chun Lu ◽  
Wangfeng Zhou ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Lung Tissue ◽  
Inflammatory Diseases ◽  
Inflammatory Cells ◽  
Genes Expression ◽  
Tnf Α ◽  
Induced Changes

Acute lung injury (ALI) is the leading cause of mortality in the intensive care unit. Currently, there is no effective pharmacological treatment for ALI. In our previous study, we reported that Lg25 and Lg26, two indole-2-carboxamide derivatives, inhibited the lipopolysaccharide (LPS)-induced inflammatory cytokines in vitro and attenuated LPS-induced sepsis in vivo. In the present study, we confirmed data from previous studies that LPS significantly induced pulmonary edema and pathological changes in lung tissue, increased protein concentration and number of inflammatory cells in bronchoalveolar lavage fluids (BALF), and increased inflammatory cytokine TNF-α expression in serum and BALF, pro-inflammatory genes expression, and macrophages infiltration in lung tissue. However, pretreatment with Lg25 and Lg26 significantly attenuated the LPS-induced changes in mice. Taken together, these data indicate that the newly discovered indole-2-carboxamide derivatives could be particularly useful in the treatment of inflammatory diseases such as ALI.

scholarly journals The metalloproteinase ADAM8 promotes leukocyte recruitment in vitro and in acute lung inflammation

2017 ◽  
Vol 313 (3) ◽  
pp. L602-L614 ◽  
Author(s):  
Daniela Dreymueller ◽  
Jessica Pruessmeyer ◽  
Julian Schumacher ◽  
Sandra Fellendorf ◽  
Franz Martin Hess ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Epithelial Cells ◽  
Lung Inflammation ◽  
Leukocyte Recruitment ◽  
Acute Lung Inflammation ◽  
Blood Leukocytes ◽  
Epithelial Layers ◽  
Deficient Mice

Alveolar leukocyte recruitment is a hallmark of acute lung inflammation and involves transmigration of leukocytes through endothelial and epithelial layers. The disintegrin and metalloproteinase (ADAM) 8 is expressed on human isolated leukocytic cells and can be further upregulated on cultured endothelial and epithelial cells by proinflammatory cytokines. By shRNA-mediated knockdown we show that leukocytic ADAM8 is required on monocytic THP-1 cells for chemokine-induced chemotaxis as well as transendothelial and transepithelial migration. Furthermore, ADAM8 promotes αL-integrin upregulation and THP-1 cell adhesion to endothelial cells. On endothelial cells ADAM8 enhances transendothelial migration and increases cytokine-induced permeability. On epithelial cells the protease facilitates migration in a wound closure assay but does not affect transepithelial leukocyte migration. Blood leukocytes and bone marrow-derived macrophages (BMDM) from ADAM8-deficient mice show suppressed chemotactic response. Intranasal application of LPS to mice is accompanied with ADAM8 upregulation in the lung. In this model of acute lung inflammation ADAM8-deficient mice are protected against leukocyte infiltration. Finally, transfer experiments of BMDM in mice indicate that ADAM8 exerts a promigratory function predominantly on leukocytes. Our study provides in vitro and in vivo evidence that ADAM8 on leukocytes holds a proinflammatory function in acute lung inflammation by promoting alveolar leukocyte recruitment.

scholarly journals Gαi2 is required for chemokine-induced neutrophil arrest

Blood ◽  
2007 ◽  
Vol 110 (10) ◽  
pp. 3773-3779 ◽  
Author(s):  
Alexander Zarbock ◽  
Tracy L. Deem ◽  
Tracy L. Burcin ◽  
Klaus Ley
Keyword(s):  
Bone Marrow ◽  
Lung Inflammation ◽  
Acute Inflammation ◽  
Leukotriene B4 ◽  
Neutrophil Recruitment ◽  
Chimeric Mice ◽  
Downstream Signaling ◽  
G Protein Coupled

Abstract Chemokines, including CXCL1, participate in neutrophil recruitment by triggering the activation of integrins, which leads to arrest from rolling. The downstream signaling pathways which lead to integrin activation and neutophil arrest following G-protein–coupled receptor engagement are incompletely understood. To test whether Gαi2 is involved, mouse neutrophils in their native whole blood were investigated in mouse cremaster postcapillary venules and in flow chambers coated with P-selectin, ICAM-1, and CXCL1. Gnai2−/− neutrophils showed significantly reduced CXCL1-induced arrest in vitro and in vivo. Similar results were obtained with leukotriene B4 (LTB4). Lethally irradiated mice reconstituted with Gnai2−/− bone marrow showed a similar defect in chemoattractant-induced arrest as that of Gnai2−/− mice. In thioglycollate-induced peritonitis and lipopolysaccaride (LPS)–induced lung inflammation, chimeric mice lacking Gαi2 in hematopoietic cells showed about 50% reduced neutrophil recruitment similar to that seen in Gnai2−/− mice. These data show that neutrophil Gαi2 is necessary for chemokine-induced arrest, which is relevant for neutrophil recruitment to sites of acute inflammation.

scholarly journals Human Umbilical Cord-Derived Mesenchymal Stem Cells Alleviate Acute Lung Injury Caused by Severe Burn via Secreting TSG-6 and Inhibiting Inflammatory Response

2020 ◽  
Author(s):  
Xiaohong Hu ◽  
Lingying Liu ◽  
Yu Wang ◽  
Zhongyuan Li ◽  
Yonghui Yu ◽  
...  
Keyword(s):  
Lung Injury ◽  
Pulmonary Function ◽  
Inflammatory Cells ◽  
Human Umbilical Cord ◽  
Ct Scanner ◽  
Severe Burn ◽  
Positive Effects ◽  
Tnf Α

Abstract Objectives To investigate whether hUC-MSCs attenuated severe burn-induced ALI and the effects were based on TSG-6 secreted from hUC-MSCs.Method Rat model was established and evaluated as follows：Anires2005 animal pulmonary function tester for pulmonary function; micro-CT scanner for lung imaging manifestations; Cytokine expression was measured by ELISA assay, both inflammatory cells infiltration and lung injury were assessed by immunohistochemistry assay.Results In vitro, TSG-6 levels in serum from burn group were significantly increased than that of the sham group. In vivo, TSG-6 levels of lung tissues and serum in burn+ hUC-MSCs group were significantly increased than that of in the burn group. Higher parameters of the airway resistance（Ri, Re, etc）were markedly decreased and the disordered lung texture and funicular density shadows were significantly improved after hUC-MSCs administration. Both in lung tissues and serum, increased levels of pro-inflammatory cytokines（TNF-α, IL-1β, IL-6）were remarkably decreased but anti-inflammatory cytokine IL-10 increased after hUC-MSCs administrations (p<0.05). These significant positive effects after hUC-MSCs transplantation did not occur in the Burn+siTSG-6 group.Conclusions Intra-tracheal implantation of hUC-MSCs had been an effective treatment for severe burn-induced ALI via promoting TSG-6 secretion and inhibiting inflammatory reaction in lung tissue.

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