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Annals of the American Thoracic Society Mar 2016Macrophages (MPs) are one of the most prominent leukocyte populations in the lung and, in many ways, a forgotten player in asthma pathogenesis. Diverse functions in... (Review)
Review
Macrophages (MPs) are one of the most prominent leukocyte populations in the lung and, in many ways, a forgotten player in asthma pathogenesis. Diverse functions in asthma initiation and maintenance in chronic disease have been demonstrated, which has led to confusion as to if pulmonary MPs are agents of good or evil in asthma. Much of this is due to the wide diversity of MP populations in the lung, many of which are inaccessible experimentally in most clinical studies. This review frames lung MP biology in the context of location, phenotype, function, and response phase in asthma pathogenesis. It also assesses new findings regarding MP diversity that have challenged old dogmas and generates new ways to understand how MPs function.
Topics: Animals; Asthma; Bronchoalveolar Lavage Fluid; Humans; Lung; Macrophages, Alveolar
PubMed: 27027949
DOI: 10.1513/AnnalsATS.201506-384MG -
Frontiers in Immunology 2023Several studies have demonstrated great potential implications for the gut-lung axis in lung disease etiology and treatment. The gut environment can be influenced by... (Review)
Review
Several studies have demonstrated great potential implications for the gut-lung axis in lung disease etiology and treatment. The gut environment can be influenced by diet, metabolites, microbiotal composition, primary diseases, and medical interventions. These changes modulate the functions of alveolar macrophages (AMs) to shape the pulmonary immune response, which greatly impacts lung health. The immune modulation of AMs is implicated in the pathogenesis of various lung diseases. However, the mechanism of the gut-lung axis in lung diseases has not yet been determined. This mini-review aimed to shed light on the critical nature of communication between the gut and AMs during the development of pulmonary infection, injury, allergy, and malignancy. A better understanding of their crosstalk may provide new insights into future therapeutic strategies targeting the gut-AM interaction.
Topics: Humans; Macrophages, Alveolar; Lung; Lung Diseases; Hypersensitivity
PubMed: 38077401
DOI: 10.3389/fimmu.2023.1279677 -
Frontiers in Immunology 2020Alveolar macrophage (AM) is a mononuclear phagocyte key to the defense against respiratory infections. To understand AM's role in airway disease development, we examined...
Alveolar macrophage (AM) is a mononuclear phagocyte key to the defense against respiratory infections. To understand AM's role in airway disease development, we examined the influence of Secretoglobin family 1a member 1 (SCGB1A1), a pulmonary surfactant protein, on AM development and function. In a murine model, high-throughput RNA-sequencing and gene expression analyses were performed on purified AMs isolated from mice lacking in gene and were compared with that from mice expressing the wild type at weaning (4 week), puberty (8 week), early adult (12 week), and middle age (40 week). AMs from early adult mice under sufficiency demonstrated a total of 37 up-regulated biological pathways compared to that at weaning, from which 30 were directly involved with antigen presentation, anti-viral immunity and inflammation. Importantly, these pathways under deficiency were significantly down-regulated compared to that in the age-matched sufficient counterparts. Furthermore, AMs from -deficient mice showed an early activation of inflammatory pathways compared with that from -sufficient mice. Our experiments with AM culture established that exogenous supplementation of SCGB1a1 protein significantly reduced AM responses to microbial stimuli where SCGB1a1 was effective in blunting the release of cytokines and chemokines (including IL-1b, IL-6, IL-8, MIP-1a, TNF-a, and MCP-1). Taken together, these findings suggest an important role for in shaping the AM-mediated inflammation and immune responses, and in mitigating cytokine surges in the lungs.
Topics: Animals; Chemokines; Cytokines; Down-Regulation; Gene Expression; Inflammation; Lung; Macrophages, Alveolar; Mice; Mice, Inbred C57BL; Mice, Knockout; Signal Transduction; Up-Regulation; Uteroglobin
PubMed: 33117399
DOI: 10.3389/fimmu.2020.584310 -
MBio Oct 2023Pneumonia caused by methicillin-resistant (MRSA) continues to carry a high burden in terms of mortality. With the roles of gut microbiota in mediating lung diseases...
Pneumonia caused by methicillin-resistant (MRSA) continues to carry a high burden in terms of mortality. With the roles of gut microbiota in mediating lung diseases being gradually uncovered, the details of the molecular mechanism of the "gut-lung axis" mediated by beneficial microorganisms and small-molecule metabolites have gradually attracted the attention of researchers. However, further studies are still necessary to determine the efficacy of microbial-based interventions. Our findings indicate that sodium butyrate (NaB) alleviates MRSA-induced pulmonary inflammation by improving gut-lung microbiota and promoting M2 polarization of alveolar macrophages. Therefore, the preventive administration of NaB might be explored as an effective strategy to control MRSA pneumonia.
Topics: Humans; Macrophages, Alveolar; Methicillin-Resistant Staphylococcus aureus; Gastrointestinal Microbiome; Lung; Pneumonia; Butyric Acid
PubMed: 37754570
DOI: 10.1128/mbio.01987-23 -
Cancer Research Jun 2023Cellular components of the tumor microenvironment, including myeloid cells, play important roles in the progression of lung adenocarcinoma (LUAD) and its response to...
UNLABELLED
Cellular components of the tumor microenvironment, including myeloid cells, play important roles in the progression of lung adenocarcinoma (LUAD) and its response to therapy. Here, we characterize the function of the ubiquitin ligases Siah1a/2 in regulating the differentiation and activity of alveolar macrophages (AM) and assess the implication of Siah1a/2 control of AMs for carcinogen-induced LUAD. Macrophage-specific genetic ablation of Siah1a/2 promoted accumulation of AMs with an immature phenotype and increased expression of protumorigenic and pro-inflammatory Stat3 and β-catenin gene signatures. Administration of urethane to wild-type mice promoted enrichment of immature-like AMs and lung tumor development, which was enhanced by macrophage-specific Siah1a/2 ablation. The profibrotic gene signature seen in Siah1a/2-ablated immature-like macrophages was associated with increased tumor infiltration of CD14+ myeloid cells and poorer survival of patients with LUAD. Single-cell RNA-seq confirmed the presence of a cluster of immature-like AMs expressing a profibrotic signature in lungs of patients with LUAD, a signature enhanced in smokers. These findings identify Siah1a/2 in AMs as gatekeepers of lung cancer development.
SIGNIFICANCE
The ubiquitin ligases Siah1a/2 control proinflammatory signaling, differentiation, and profibrotic phenotypes of alveolar macrophages to suppress lung carcinogenesis.
Topics: Animals; Mice; Macrophages, Alveolar; Adenocarcinoma of Lung; Lung Neoplasms; Tumor Microenvironment; Ubiquitin-Protein Ligases; Male; Mice, Inbred C57BL; Mice, Knockout
PubMed: 37078793
DOI: 10.1158/0008-5472.CAN-23-0258 -
Inflammation Research : Official... Dec 2022Acute respiratory distress syndrome (ARDS) is an acute and diffuse inflammatory lung injury in a short time, one of the common severe manifestations of the respiratory... (Review)
Review
Acute respiratory distress syndrome (ARDS) is an acute and diffuse inflammatory lung injury in a short time, one of the common severe manifestations of the respiratory system that endangers human life and health. As an innate immune cell, macrophages play a key role in the inflammatory response. For a long time, the role of pulmonary macrophages in ARDS has tended to revolve around the polarization of M1/M2. However, with the development of single-cell RNA sequencing, fate mapping, metabolomics, and other new technologies, a deeper understanding of the development process, classification, and function of macrophages in the lung are acquired. Here, we discuss the function of pulmonary macrophages in ARDS from the two dimensions of anatomical location and cell origin and describe the effects of cell metabolism and intercellular interaction on the function of macrophages. Besides, we explore the treatments for targeting macrophages, such as enhancing macrophage phagocytosis, regulating macrophage recruitment, and macrophage death. Considering the differences in responsiveness of different research groups to these treatments and the tremendous dynamic changes in the gene expression of monocyte/macrophage, we discussed the possibility of characterizing the gene expression of monocyte/macrophage as the biomarkers. We hope that this review will provide new insight into pulmonary macrophage function and therapeutic targets of ARDS.
Topics: Humans; Macrophages, Alveolar; Acute Lung Injury; Respiratory Distress Syndrome; Macrophages; Lung
PubMed: 36264361
DOI: 10.1007/s00011-022-01645-4 -
Seminars in Immunology Dec 2014Macrophages, the major host cells harboring Mycobacterium tuberculosis (M.tb), are a heterogeneous cell type depending on their tissue of origin and host they are... (Review)
Review
Macrophages, the major host cells harboring Mycobacterium tuberculosis (M.tb), are a heterogeneous cell type depending on their tissue of origin and host they are derived from. Significant discord in macrophage responses to M.tb exists due to differences in M.tb strains and the various types of macrophages used to study tuberculosis (TB). This review will summarize current concepts regarding macrophage responses to M.tb infection, while pointing out relevant differences in experimental outcomes due to the use of divergent model systems. A brief description of the lung environment is included since there is increasing evidence that the alveolar macrophage (AM) has immunoregulatory properties that can delay optimal protective host immune responses. In this context, this review focuses on selected macrophage immunoregulatory pattern recognition receptors (PRRs), cytokines, negative regulators of inflammation, lipid mediators and microRNAs (miRNAs).
Topics: Cytokines; Gene Expression Regulation; Host-Pathogen Interactions; Humans; Immunity, Innate; Lung; Macrophage Activation; Macrophages, Alveolar; MicroRNAs; Mycobacterium tuberculosis; Receptors, Pattern Recognition; Tuberculosis, Pulmonary
PubMed: 25453226
DOI: 10.1016/j.smim.2014.09.010 -
Frontiers in Immunology 2023Acute respiratory distress syndrome (ARDS) is associated with high mortality rates in patients admitted to the intensive care unit (ICU) patients with overwhelming...
Acute respiratory distress syndrome (ARDS) is associated with high mortality rates in patients admitted to the intensive care unit (ICU) patients with overwhelming inflammation considered to be an internal cause. The authors' previous study indicated a potential correlation between phenylalanine levels and lung injury. Phenylalanine induces inflammation by enhancing the innate immune response and the release of pro-inflammatory cytokines. Alveolar macrophages (AMs) can respond to stimuli synthesis and release of inflammatory mediators through pyroptosis, one form of programmed cell death acting through the nucleotide-binging oligomerization domain-like receptors protein 3 (NLRP3) signaling pathway, resulting in the cleavage of caspase-1 and gasdermin D (GSDMD) and the release of interleukin (IL) -1β and IL-18, aggravating lung inflammation and injury in ARDS. In this study, phenylalanine promoted pyroptosis of AMs, which exacerbated lung inflammation and ARDS lethality in mice. Furthermore, phenylalanine initiated the NLRP3 pathway by activating the calcium-sensing receptor (CaSR). These findings uncovered a critical mechanism of action of phenylalanine in the context of ARDS and may be a new treatment target for ARDS.
Topics: Animals; Mice; Macrophages, Alveolar; Pyroptosis; NLR Family, Pyrin Domain-Containing 3 Protein; Receptors, Calcium-Sensing; Phenylalanine; Respiratory Distress Syndrome; Pneumonia; Inflammation
PubMed: 37377971
DOI: 10.3389/fimmu.2023.1114129 -
BioMed Research International 2014An alcohol use disorder increases the risk of invasive and antimicrobial resistant community-acquired pneumonia and tuberculosis. Since the alveolar macrophage (AM)...
An alcohol use disorder increases the risk of invasive and antimicrobial resistant community-acquired pneumonia and tuberculosis. Since the alveolar macrophage (AM) orchestrates the immune response in the alveolar space, understanding the underlying mechanisms by which alcohol suppresses AM phagocytosis is critical to improving clinical outcomes. In the alveolar space, chronic alcohol ingestion causes severe oxidative stress and depletes antioxidants which are critical for AM function. The mitochondrion is important in maintaining cellular redox balance and providing the ATP critical for phagocytosis. The focus of this study was to understand how alcohol triggers mitochondrial reactive oxygen species (ROS), stimulates cellular oxidative stress, and induces AM dysfunction. The current study also investigated the capacity of the mitochondrial targeted antioxidant, mitoTEMPOL (mitoT), in modulating mitochondrial oxidative stress, and AM dysfunction. Using in vitro ethanol exposure and AMs from ethanol-fed mice, ethanol promoted mitochondrial dysfunction including increased mitochondrial ROS, decreased mitochondrial membrane potential, and decreased ATP. Treatment with mitoT reversed these effects. Ethanol-induced decreases in phagocytosis and cell viability were also attenuated with mitoT. Therefore, antioxidants targeted to the mitochondria have the potential to ameliorate ethanol-induced mitochondrial oxidative stress and subsequent decreases in AM phagocytosis and cell viability.
Topics: Alcoholism; Animals; Cell Survival; Ethanol; Humans; Macrophages, Alveolar; Mice; Mitochondria; Oxidative Stress; Phagocytosis; Pulmonary Alveoli; Reactive Oxygen Species
PubMed: 24701574
DOI: 10.1155/2014/371593 -
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