M2 macrophage accumulation contributes to pulmonary fibrosis, vascular dilatation, and hypoxemia in rat hepatopulmonary syndrome

2021 ◽  
Author(s):  
Bing Chen ◽  
Yong Yang ◽  
Congwen Yang ◽  
Jiaxiang Duan ◽  
Lin Chen ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Hepatopulmonary Syndrome ◽  
M2 Macrophage ◽  
Vascular Dilatation ◽  
Macrophage Accumulation

scholarly journals MBD2 serves as a viable target against pulmonary fibrosis by inhibiting macrophage M2 program

2020 ◽  
Vol 7 (1) ◽  
pp. eabb6075
Author(s):  
Yi Wang ◽  
Lei Zhang ◽  
Guo-Rao Wu ◽  
Qing Zhou ◽  
Huihui Yue ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β1 ◽  
M2 Macrophage ◽  
Clinical Settings ◽  
Intratracheal Administration ◽  
Different Types ◽  
Lung Injuries ◽  
Tgf Β1 ◽  
Macrophage Accumulation

Despite past extensive studies, the mechanisms underlying pulmonary fibrosis (PF) still remain poorly understood. Here, we demonstrated that lungs originating from different types of patients with PF, including coronavirus disease 2019, systemic sclerosis–associated interstitial lung disease, and idiopathic PF, and from mice following bleomycin (BLM)–induced PF are characterized by the altered methyl-CpG–binding domain 2 (MBD2) expression in macrophages. Depletion of Mbd2 in macrophages protected mice against BLM-induced PF. Mbd2 deficiency significantly attenuated transforming growth factor–β1 (TGF-β1) production and reduced M2 macrophage accumulation in the lung following BLM induction. Mechanistically, Mbd2 selectively bound to the Ship promoter in macrophages, by which it repressed Ship expression and enhanced PI3K/Akt signaling to promote the macrophage M2 program. Therefore, intratracheal administration of liposomes loaded with Mbd2 siRNA protected mice from BLM-induced lung injuries and fibrosis. Together, our data support the possibility that MBD2 could be a viable target against PF in clinical settings.

Hepatopulmonary syndrome as the first and only manifestation of cirrhosis in a patient with hypopituitarism

2021 ◽  
Vol 14 (9) ◽  
pp. e244805
Author(s):  
Eman Alabsawy ◽  
Yassen Serry ◽  
Sreelakshmi Kotha ◽  
Philip Berry ◽  
Giovanni Tritto
Keyword(s):  
Liver Disease ◽  
Fatty Liver Disease ◽  
Hepatopulmonary Syndrome ◽  
Progressive Dyspnoea ◽  
Alcoholic Fatty Liver ◽  
End Stage Liver Disease ◽  
Pituitary Dysfunction ◽  
Vascular Dilatation ◽  
End Stage ◽  
Alcoholic Fatty Liver Disease

Hepatopulmonary syndrome (HPS) is characterised by the development of intrapulmonary arteriovenous blood shunts and vascular dilatation with consequent hypoxaemia, usually in the context of end-stage liver disease (ESLD). The estimated incidence of HPS in ESLD has been reported to be 13%–47%. Chronic liver disease has been described in patients with hypothalamic–pituitary dysfunction, mainly in the form of non-alcoholic fatty liver disease due to metabolic syndrome, with occasional progression to cirrhosis. We report a challenging case of a 27-year-old man with a background of hypopituitarism with no known liver disease who presented with progressive dyspnoea and hypoxaemia and was eventually diagnosed with severe HPS.

Correlation of Pulmonary Vascular Dilatation on HRCT to Expression of eNOS in a Rabbit Model of Hepatopulmonary Syndrome

2001 ◽  
Vol 44 (4) ◽  
pp. 475 ◽  
Author(s):  
Ki Nam Lee ◽  
Won Jung Jung ◽  
Seong Kuk Yoon ◽  
Kyung Jin Nam ◽  
Jong Young Kwak ◽  
...  
Keyword(s):  
Rabbit Model ◽  
Hepatopulmonary Syndrome ◽  
Vascular Dilatation

scholarly journals Hepatopulmonary syndrome: an update

2009 ◽  
Vol 127 (4) ◽  
pp. 223-230 ◽  
Author(s):  
Liana Gonçalves de Macêdo ◽  
Edmundo Pessoa de Almeida Lopes
Keyword(s):  
Liver Transplantation ◽  
Contrast Echocardiography ◽  
Hepatopulmonary Syndrome ◽  
Cochrane Library ◽  
Microvascular Remodeling ◽  
Vascular Dilatation ◽  
Cirrhotic Patients ◽  
Transplant Candidates ◽  
Liver Transplant Waiting List ◽  
Worse Prognosis

Hepatopulmonary syndrome (HPS) is a clinical threesome composed of liver disease, intrapulmonary vascular dilatation (IPVD) and arterial gas abnormalities. Its occurrence has been described in up to 32% of cirrhotic candidates for liver transplantation. It also affects non-cirrhotic patients with portal hypertension. Its pathogenesis is not well defined, but an association of factors such as imbalance in the endothelin receptor response, pulmonary microvascular remodeling and genetic predisposition is thought to lead to IPVD. Diagnosis is based on imaging methods that identify these dilatations, such as contrast echocardiography or perfusion scintigraphy with 99mTc, as well as analysis of arterial gases to identify elevated alveolar-arterial differences in O2 or hypoxemia. There is no effective pharmacological treatment and complete resolution only occurs through liver transplantation. The importance of diagnosing HPS lies in prioritizing transplant candidates, since presence of HPS is associated with worse prognosis. The aim of this paper was to review the pathogenetic theories and current diagnostic criteria regarding HPS, and to critically analyze the prioritization of patients with HPS on the liver transplant waiting list. Searches were carried out in the Medline (Medical Literature Analysis and Retrieval System Online) via PubMed, Cochrane Library and Lilacs (Literatura Latino-Americana e do Caribe em Ciências da Saúde) databases for articles published between January 2002 and December 2007 involving adults and written either in English or in Portuguese, using the term hepatopulmonary syndrome. The studies of greatest relevance were included in the review, along with text books and articles cited in references that were obtained through the review.

scholarly journals Advances in Diagnostic Imaging of Hepatopulmonary Syndrome

2022 ◽  
Vol 8 ◽  
Author(s):  
Bi-Wei Luo ◽  
Zhi-Yong Du
Keyword(s):  
Liver Disease ◽  
Pulmonary Complication ◽  
Hepatopulmonary Syndrome ◽  
Pulmonary Angiography ◽  
Pulmonary Perfusion ◽  
Clinical Prognosis ◽  
Vascular Dilatation ◽  
Progressive Liver Disease ◽  
Poor Clinical Prognosis ◽  
Timely Treatment

Hepatopulmonary syndrome (HPS) is a serious pulmonary complication of progressive liver disease that leads to a poor clinical prognosis. Patients with HPS may develop acute respiratory failure, which requires intensive care and therapy. At present, the only effective treatment is liver transplantation; therefore, early diagnosis and timely treatment are of considerable significance. The three main features of HPS are liver disease, oxygenation disorder, and intrapulmonary vascular dilatation (IPVD). Diagnosing HPS is challenging due to the difficulty in detecting the presence or absence of IPVD. As such, imaging examination is very important for detecting IPVD. This paper reviews the imaging methods for diagnosing HPS such as ultrasound, dynamic pulmonary perfusion imaging, pulmonary angiography, and computed tomography.

M2 macrophages have unique transcriptomes but conditioned media does not promote profibrotic responses in lung fibroblasts or alveolar epithelial cells in vitro

2021 ◽  
Author(s):  
Elissa M Hult ◽  
Stephen James Gurczynski ◽  
Bethany B Moore
Keyword(s):  
Pulmonary Fibrosis ◽  
Alveolar Epithelial Cell ◽  
Conditioned Media ◽  
Alveolar Epithelial Cells ◽  
Lung Fibroblasts ◽  
M2 Macrophage ◽  
M2 Macrophages ◽  
Alveolar Epithelial ◽  
Fibroblast Migration

Macrophages are critical regulators of pulmonary fibrosis. Their plasticity, proximity, and ability to crosstalk with structural cells of the lung make them a key cell type of interest in the regulation of lung fibrosis. Macrophages can express a variety of phenotypes which have been historically represented through an "M1-like" to "M2-like" delineation. In this classification, M1-like macrophages are proinflammatory and have increased phagocytic capacity compared to alternatively activated M2-like macrophages that are profibrotic and are associated with wound healing. Extensive evidence in the field in both patients and animal models align pulmonary fibrosis with M2 macrophages. In this paper, we performed RNAseq to fully characterize M1 vs. M2-skewed bone marrow-derived macrophages (BMDMs) and investigated the profibrotic abilities of M2 BMDM conditioned media (CM) to promote fibroblast migration, proliferation, alveolar epithelial cell (AEC) apoptosis, and mRNA expression of key fibrotic genes in both fibroblasts and in AECs. Although M2 CM-treated fibroblasts had increased migration and M2 CM-treated fibroblasts and AECs had increased expression of profibrotic proteins over M1 CM-treated cells, all differences can be attributed to M2 polarization reagents IL-4 and IL-13 also present in the CM. Collectively, these data suggest that the profibrotic effects associated with M2 macrophage CM in vitro are attributable to effects of polarization cytokines rather than additional factors secreted in response to those polarizing cytokines.

DPP-4 Inhibition with Anagliptin Reduces Lipotoxicity-Induced Insulin Resistance and Steatohepatitis in Male Mice

Endocrinology ◽  
2020 ◽  
Vol 161 (10) ◽  
Author(s):  
Yuriko Sakai ◽  
Guanliang Chen ◽  
Yinhua Ni ◽  
Fen Zhuge ◽  
Liang Xu ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Immune System ◽  
Cell Types ◽  
Hepatic Insulin Resistance ◽  
M2 Macrophage ◽  
High Fat ◽  
Hepatic Lipid ◽  
Dipeptidyl Peptidase 4 ◽  
M1 Macrophage ◽  
Macrophage Accumulation

Abstract Excessive hepatic lipid accumulation drives the innate immune system and aggravates insulin resistance, hepatic inflammation, and fibrogenesis, leading to nonalcoholic steatohepatitis (NASH). Dipeptidyl peptidase-4 (DPP-4) regulates glucose metabolism and is expressed in many different cell types, including the cells of the immune system. In addition, DPP-4 may be involved in macrophage-mediated inflammation and insulin resistance. This study investigated the effects of anagliptin (Ana), an inhibitor of DPP-4, on macrophage polarity and phenotype in the livers of mice with steatohepatitis. We investigated the effects of Ana on steatohepatitis induced via a high-cholesterol high-fat (CL) diet or a choline-deficient L-amino acid-defined, high-fat (CDAHF) diet. DPP-4 activity, liver histology, and insulin sensitivity were evaluated, and liver DPP-4+ macrophages were quantified using fluorescence-activated cell sorting (FACS). Liver and plasma DPP-4 activity increased significantly in mice on both diets. FACS revealed that, compared with chow-fed mice, the CL-fed mice exhibited a significant increase in the proportion of DPP-4+ liver macrophages, particularly the M1-type macrophages. Ana decreased hepatic lipid and M1 macrophage accumulation and stimulated M2 macrophage accumulation in the liver, thereby attenuating insulin resistance, steatohepatitis, and fibrosis. Importantly, Ana alleviated hepatic fibrosis and steatohepatitis in mice fed CL diet and CDAHF diet. Using Ana to inhibit DPP-4 reduced lipotoxicity-induced hepatic insulin resistance through regulating the M1/M2 macrophage status.

scholarly journals Roles of Macrophage Polarization and Macrophage-Derived miRNAs in Pulmonary Fibrosis

2021 ◽  
Vol 12 ◽  
Author(s):  
Amit Kishore ◽  
Martin Petrek
Keyword(s):  
Pulmonary Fibrosis ◽  
Tissue Injury ◽  
Macrophage Polarization ◽  
Future Perspective ◽  
Current Evidence ◽  
M2 Macrophage ◽  
Cellular Mirnas ◽  
Exosomal Mirnas ◽  
Macrophage Populations ◽  
And Function

This mini-review summarizes the current evidence for the role of macrophage activation and polarization in inflammation and immune response pertinent to interstitial lung disease, specifically pulmonary fibrosis. In the fibrosing lung, the production and function of inflammatory and fibrogenic mediators involved in the disease development have been reported to be regulated by the effects of polarized M1/M2 macrophage populations. The M1 and M2 macrophage phenotypes were suggested to correspond with the pro-inflammatory and pro-fibrogenic signatures, respectively. These responses towards tissue injury followed by the development and progression of lung fibrosis are further regulated by macrophage-derived microRNAs (miRNAs). Besides cellular miRNAs, extracellular exosomal-miRNAs derived from M2 macrophages have also been proposed to promote the progression of pulmonary fibrosis. In a future perspective, harnessing the noncoding miRNAs with a key role in the macrophage polarization is, therefore, suggested as a promising therapeutic strategy for this debilitating disease.

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