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Seminars in Immunopathology Jul 2016Alveolar macrophages have been investigated for years by approaches involving macrophage extraction from the lung by bronchoalveolar lavage, or by cell removal from lung... (Review)
Review
Alveolar macrophages have been investigated for years by approaches involving macrophage extraction from the lung by bronchoalveolar lavage, or by cell removal from lung tissue. Since extracted macrophages are studied outside their natural milieu, there is little understanding of the extent to which alveolar macrophages interact with the epithelium, or with one another to generate the lung's innate immune response to pathogen challenge. Here, we review new evidence of macrophage-epithelial interactions in the lung, and we address the emerging understanding that the alveolar epithelium plays an important role in orchestrating the macrophage-driven immune response.
Topics: Alveolar Epithelial Cells; Animals; Biomarkers; Calcium; Cell Communication; Cytokines; Gap Junctions; Homeostasis; Humans; Inflammation Mediators; Macrophages, Alveolar; Pneumonia; Pulmonary Alveoli; Signal Transduction
PubMed: 27170185
DOI: 10.1007/s00281-016-0569-x -
Frontiers in Immunology 2022Pulmonary macrophages have two distinct ontogenies: long-lived embryonically-seeded alveolar macrophages (AM) and bone marrow-derived macrophages (BMDM). Here, we show...
Pulmonary macrophages have two distinct ontogenies: long-lived embryonically-seeded alveolar macrophages (AM) and bone marrow-derived macrophages (BMDM). Here, we show that after infection with a virulent strain of (H37Rv), primary murine AM exhibit a unique transcriptomic signature characterized by metabolic reprogramming distinct from conventional BMDM. In contrast to BMDM, AM failed to shift from oxidative phosphorylation (OXPHOS) to glycolysis and consequently were unable to control infection with an avirulent strain (H37Ra). Importantly, healthy human AM infected with H37Ra equally demonstrated diminished energetics, recapitulating our observation in the murine model system. However, the results from seahorse showed that the shift towards glycolysis in both AM and BMDM was inhibited by H37Rv. We further demonstrated that pharmacological (e.g. metformin or the iron chelator desferrioxamine) reprogramming of AM towards glycolysis reduced necrosis and enhanced AM capacity to control H37Rv growth. Together, our results indicate that the unique bioenergetics of AM renders these cells a perfect target for survival and that metabolic reprogramming may be a viable host targeted therapy against TB.
Topics: Humans; Animals; Mice; Macrophages, Alveolar; Tuberculosis; Mycobacterium tuberculosis; Macrophages; Necrosis
PubMed: 36776396
DOI: 10.3389/fimmu.2022.1044592 -
International Journal of Molecular... Jan 2021Silicosis is an urgent public health problem in many countries. Alveolar macrophage (AM) plays an important role in silicosis progression. Autophagy is a balanced... (Review)
Review
Silicosis is an urgent public health problem in many countries. Alveolar macrophage (AM) plays an important role in silicosis progression. Autophagy is a balanced mechanism for regulating the cycle of synthesis and degradation of cellular components. Our previous study has shown that silica engulfment results in lysosomal rupture, which may lead to the accumulation of autophagosomes in AMs of human silicosis. The excessive accumulation of autophagosomes may lead to apoptosis in AMs. Herein, we addressed some assumptions concerning the complex function of autophagy-related proteins on the silicosis pathogenesis. We also recapped the molecular mechanism of several critical proteins targeting macrophage autophagy in the process of silicosis fibrosis. Furthermore, we summarized several exogenous chemicals that may cause an aggravation or alleviation for silica-induced pulmonary fibrosis by regulating AM autophagy. For example, lipopolysaccharides or nicotine may have a detrimental effect combined together with silica dust via exacerbating the blockade of AM autophagic degradation. Simultaneously, some natural product ingredients such as atractylenolide III, dioscin, or trehalose may be the potential AM autophagy regulators, protecting against silicosis fibrosis. In conclusion, the deeper molecular mechanism of these autophagy targets should be explored in order to provide feasible clues for silicosis therapy in the clinical setting.
Topics: Animals; Autophagy; Humans; Lysosomes; Macrophages, Alveolar; Pulmonary Fibrosis; Silicosis
PubMed: 33466366
DOI: 10.3390/ijms22010453 -
Frontiers in Immunology 2023
Topics: Lung; Macrophages, Alveolar
PubMed: 38045688
DOI: 10.3389/fimmu.2023.1332852 -
Frontiers in Immunology 2020Circulating inflammatory monocytes are attracted to infected mucosa and differentiate into macrophage or dendritic cells endowed with enhanced bactericidal and antigen... (Review)
Review
Circulating inflammatory monocytes are attracted to infected mucosa and differentiate into macrophage or dendritic cells endowed with enhanced bactericidal and antigen presenting capacities. In this brief Perspective we discuss the newly emerging insight into how the cAMP signaling capacity of adenylate cyclase toxin manipulates the differentiation of monocytes and trigger dedifferentiation of the alveolar macrophages to facilitate bacterial colonization of human airways.
Topics: Adenylate Cyclase Toxin; Animals; Antigen Presentation; Bordetella pertussis; Cell Dedifferentiation; Cell Differentiation; Cyclic AMP; Host-Pathogen Interactions; Humans; Immunity, Innate; Immunity, Mucosal; Macrophages, Alveolar; Mice; Models, Biological; Monocytes; Phagocytosis; Respiratory System; Second Messenger Systems
PubMed: 33013916
DOI: 10.3389/fimmu.2020.02181 -
Journal of Lipid Research Feb 2024Pulmonary alveolar proteinosis (PAP) is a life-threatening, rare lung syndrome for which there is no cure and no approved therapies. PAP is a disease of lipid...
Pulmonary alveolar proteinosis (PAP) is a life-threatening, rare lung syndrome for which there is no cure and no approved therapies. PAP is a disease of lipid accumulation characterized by alveolar macrophage foam cell formation. While much is known about the clinical presentation, there is a paucity of information regarding temporal changes in lipids throughout the course of disease. Our objectives were to define the detailed lipid composition of alveolar macrophages in PAP patients at the time of diagnosis and during treatment. We performed comprehensive mass spectrometry to profile the lipid signature of alveolar macrophages obtained from three independent mouse models of PAP and from PAP and non-PAP patients. Additionally, we quantified changes in macrophage-associated lipids during clinical treatment of PAP patients. We found remarkable variations in lipid composition in PAP patients, which were consistent with data from three independent mouse models. Detailed lipidomic analysis revealed that the overall alveolar macrophage lipid burden inversely correlated with clinical improvement and response to therapy in PAP patients. Specifically, as PAP patients experienced clinical improvement, there was a notable decrease in the total lipid content of alveolar macrophages. This crucial observation suggests that the levels of these macrophage-associated lipids can be utilized to assess the efficacy of treatment. These findings provide valuable insights into the dysregulated lipid metabolism associated with PAP, offering the potential for lipid profiling to serve as a means of monitoring therapeutic interventions in PAP patients.
Topics: Animals; Mice; Humans; Pulmonary Alveolar Proteinosis; Macrophages, Alveolar; Lung; Macrophages; Lipids
PubMed: 38185217
DOI: 10.1016/j.jlr.2024.100496 -
JCI Insight Mar 2022Recovery from pneumococcal pneumonia remodels the pool of alveolar macrophages so that they exhibit new surface marker profiles, transcriptomes, metabolomes, and...
Recovery from pneumococcal pneumonia remodels the pool of alveolar macrophages so that they exhibit new surface marker profiles, transcriptomes, metabolomes, and responses to infection. Mechanisms mediating alveolar macrophage phenotypes after pneumococcal pneumonia have not been delineated. IFN-γ and its receptor on alveolar macrophages were essential for certain, but not all, aspects of the remodeled alveolar macrophage phenotype. IFN-γ was produced by CD4+ T cells plus other cells, and CD4+ cell depletion did not prevent alveolar macrophage remodeling. In mice infected or recovering from pneumococcus, monocytes were recruited to the lungs, and the monocyte-derived macrophages developed characteristics of alveolar macrophages. CCR2 mediated the early monocyte recruitment but was not essential to the development of the remodeled alveolar macrophage phenotype. Lineage tracing demonstrated that recovery from pneumococcal pneumonias converted the pool of alveolar macrophages from being primarily of embryonic origin to being primarily of adult hematopoietic stem cell origin. Alveolar macrophages of either origin demonstrated similar remodeled phenotypes, suggesting that ontogeny did not dictate phenotype. Our data reveal that the remodeled alveolar macrophage phenotype in lungs recovered from pneumococcal pneumonia results from a combination of new recruitment plus training of both the original cells and the new recruits.
Topics: Animals; Lung; Macrophages; Macrophages, Alveolar; Mice; Monocytes; Pneumonia, Pneumococcal
PubMed: 35133985
DOI: 10.1172/jci.insight.150239 -
Medicine Sep 2023Alveolar macrophage phagocytosis is significantly reduced in Chronic obstructive pulmonary disease, and cigarette smoke extract is one of the chief reasons for this...
Alveolar macrophage phagocytosis is significantly reduced in Chronic obstructive pulmonary disease, and cigarette smoke extract is one of the chief reasons for this decrease. Nevertheless, the specific underlying mechanism remains elusive. In this study, the role and possible mechanism of miR-155-5p/mTORC2/RhoA in the phagocytosis of mouse alveolar macrophages (MH-S) were explored. Our results revealed that cigarette smoke extract intervention reduced MH-S cell phagocytosis and miR-155-5p expression. Meanwhile, the dual-luciferase reporter assay validated that Rictor is a target of miR-155-5p. On the one hand, transfecting miR-155-5p mimic, mimic NC, miR-155-5p inhibitor, or inhibitor NC in MH-S cells overexpressing miR-155-5p increased the Alveolar macrophage phagocytotic rate, up-regulated the expression level of RhoA and p-RhoA, and down-regulated that of mTOR and Rictor mRNA and protein. On the other hand, inhibiting the expression of miR-155-5p lowered the phagocytotic rate, up-regulated the expression of mTOR, Rictor mRNA, and protein, and down-regulated the expression of RhoA and p-RhoA, which taken together, authenticated that miR-155-5p participates in macrophage phagocytosis via the mTORC2/RhoA pathway. Finally, confocal microscopy demonstrated that cells overexpressing miR-155-5p underwent cytoskeletal rearrangement during phagocytosis, and the phagocytic function of cells was enhanced, signaling that miR-155-5p participated in macrophage skeletal rearrangement and enhanced alveolar macrophage phagocytosis by targeting the expression of Rictor in the mTORC2/RhoA pathway.
Topics: Animals; Mice; Macrophages, Alveolar; Mechanistic Target of Rapamycin Complex 2; MicroRNAs; Phagocytosis; RNA, Messenger; TOR Serine-Threonine Kinases; Transcription Factors; Signal Transduction
PubMed: 37657048
DOI: 10.1097/MD.0000000000034592 -
Cells May 2024Pulmonary surfactants play a crucial role in managing lung lipid metabolism, and dysregulation of this process is evident in various lung diseases. Alternations in lipid... (Review)
Review
Pulmonary surfactants play a crucial role in managing lung lipid metabolism, and dysregulation of this process is evident in various lung diseases. Alternations in lipid metabolism lead to pulmonary surfactant damage, resulting in hyperlipidemia in response to lung injury. Lung macrophages are responsible for recycling damaged lipid droplets to maintain lipid homeostasis. The inflammatory response triggered by external stimuli such as cigarette smoke, bleomycin, and bacteria can interfere with this process, resulting in the formation of lipid-laden macrophages (LLMs), also known as foamy macrophages. Recent studies have highlighted the potential significance of LLM formation in a range of pulmonary diseases. Furthermore, growing evidence suggests that LLMs are present in patients suffering from various pulmonary conditions. In this review, we summarize the essential metabolic and signaling pathways driving the LLM formation in chronic obstructive pulmonary disease, pulmonary fibrosis, tuberculosis, and acute lung injury.
Topics: Humans; Lung Diseases; Lipid Metabolism; Animals; Macrophages; Macrophages, Alveolar; Signal Transduction
PubMed: 38891022
DOI: 10.3390/cells13110889 -
Alcohol (Fayetteville, N.Y.) Sep 2016Annually, excessive alcohol use accounts for more than $220 billion in economic costs and 80,000 deaths, making excessive alcohol use the third leading lifestyle-related... (Review)
Review
Annually, excessive alcohol use accounts for more than $220 billion in economic costs and 80,000 deaths, making excessive alcohol use the third leading lifestyle-related cause of death in the US. Patients with an alcohol-use disorder (AUD) also have an increased susceptibility to respiratory pathogens and lung injury, including a 2-4-fold increased risk of acute respiratory distress syndrome (ARDS). This review investigates some of the potential mechanisms by which alcohol causes lung injury and impairs lung immunity. In intoxicated individuals with burn injuries, activation of the gut-liver axis drives pulmonary inflammation, thereby negatively impacting morbidity and mortality. In the lung, the upper airway is the first checkpoint to fail in microbe clearance during alcohol-induced lung immune dysfunction. Brief and prolonged alcohol exposure drive different post-translational modifications of novel proteins that control cilia function. Proteomic approaches are needed to identify novel alcohol targets and post-translational modifications in airway cilia that are involved in alcohol-dependent signal transduction pathways. When the upper airway fails to clear inhaled pathogens, they enter the alveolar space where they are primarily cleared by alveolar macrophages (AM). With chronic alcohol ingestion, oxidative stress pathways in the AMs are stimulated, thereby impairing AM immune capacity and pathogen clearance. The epidemiology of pneumococcal pneumonia and AUDs is well established, as both increased predisposition and illness severity have been reported. AUD subjects have increased susceptibility to pneumococcal pneumonia infections, which may be due to the pro-inflammatory response of AMs, leading to increased oxidative stress.
Topics: Alcohol Drinking; Animals; Ethanol; Gastrointestinal Tract; Humans; Immunity, Cellular; Lung Injury; Macrophages, Alveolar; Oxidative Stress
PubMed: 27788778
DOI: 10.1016/j.alcohol.2016.08.005