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Respiratory Research Mar 2018Acute lung injury (ALI) and its severe form, known as acute respiratory distress syndrome (ARDS), are caused by direct pulmonary insults and indirect systemic... (Review)
Review
Acute lung injury (ALI) and its severe form, known as acute respiratory distress syndrome (ARDS), are caused by direct pulmonary insults and indirect systemic inflammatory responses that result from conditions such as sepsis, trauma, and major surgery. The reciprocal influences between pulmonary and systemic inflammation augments the inflammatory process in the lung and promotes the development of ALI. Emerging evidence has revealed that alveolar macrophage (AM) death plays important roles in the progression of lung inflammation through its influence on other immune cell populations in the lung. Cell death and tissue inflammation form a positive feedback cycle, ultimately leading to exaggerated inflammation and development of disease. Pharmacological manipulation of AM death signals may serve as a logical therapeutic strategy for ALI/ARDS. This review will focus on recent advances in the regulation and underlying mechanisms of AM death as well as the influence of AM death on the development of ALI.
Topics: Acute Lung Injury; Animals; Cell Death; Humans; Macrophages, Alveolar; Pneumonia; Respiratory Distress Syndrome; Signal Transduction
PubMed: 29587748
DOI: 10.1186/s12931-018-0756-5 -
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 -
Experimental Cell Research Sep 2019Neutrophils activated during acute lung injury (ALI) form neutrophil extracellular traps (NETs) to capture pathogens. However, excessive NETs can cause severe...
Neutrophils activated during acute lung injury (ALI) form neutrophil extracellular traps (NETs) to capture pathogens. However, excessive NETs can cause severe inflammatory reactions. Macrophages are classified as M1 macrophages with proinflammatory effects or M2 macrophages with anti-inflammatory effects. During ALI, alveolar macrophages (AMs) polarize to the M1 phenotype. This study tested the hypothesis that NETs may aggravate ALI or acute respiratory distress syndrome (ARDS) inflammation by promoting alveolar macrophage polarization to the M1 type. Our research was carried out in three aspects: clinical research, animal experiments and in vitro experiments. We determined that NET levels in ARDS patients were positively correlated with M1-like macrophage polarization. NET formation was detected in murine ALI tissue and associated with increased M1 markers and decreased M2 markers in BALF and lung tissue. Treatment with NET inhibitors significantly inhibitor NETs generation, downregulated M1 markers and upregulated M2 markers. Regardless of LPS pre-stimulation, significant secretion of proinflammatory cytokines and upregulated M1 markers were detected from bone marrow-derived macrophages (M0 and M2) cocultured with high concentrations of NETs; conversely, M2 markers were downregulated. In conclusion, NETs promote ARDS inflammation during the acute phase by promoting macrophage polarization to the M1 phenotype. We propose that NETs play an important role in the interaction between neutrophils and macrophages during the early acute phase of ALI.
Topics: Acute Lung Injury; Animals; Cell Polarity; Extracellular Traps; Female; Lipopolysaccharides; Macrophages, Alveolar; Mice, Inbred C57BL; Respiratory Distress Syndrome
PubMed: 31255598
DOI: 10.1016/j.yexcr.2019.06.031 -
Molecules and Cells May 2021Macrophages residing in various tissue types are unique in terms of their anatomical locations, ontogenies, developmental pathways, gene expression patterns, and... (Review)
Review
Macrophages residing in various tissue types are unique in terms of their anatomical locations, ontogenies, developmental pathways, gene expression patterns, and immunological functions. Alveolar macrophages (AMs) reside in the alveolar lumen of the lungs and serve as the first line of defense for the respiratory tract. The immunological functions of AMs are implicated in the pathogenesis of various pulmonary diseases such as allergic asthma, chronic obstructive pulmonary disorder (COPD), pulmonary alveolar proteinosis (PAP), viral infection, and bacterial infection. Thus, the molecular mechanisms driving the development and function of AMs have been extensively investigated. In this review article, we discuss the roles of granulocyte-macrophage colony-stimulating factor (GM-CSF) and transforming growth factor (TGF)-β in AM development, and provide an overview of the anti-inflammatory and proinflammatory functions of AMs in various contexts. Notably, we examine the relationships between the metabolic status of AMs and their development processes and functions. We hope that this review will provide new information and insight into AM development and function.
Topics: Humans; Macrophages, Alveolar
PubMed: 33972474
DOI: 10.14348/molcells.2021.0058 -
Cell Jul 2021Cytomegaloviruses (CMVs) have co-evolved with their mammalian hosts for millions of years, leading to remarkable host specificity and high infection prevalence....
Cytomegaloviruses (CMVs) have co-evolved with their mammalian hosts for millions of years, leading to remarkable host specificity and high infection prevalence. Macrophages, which already populate barrier tissues in the embryo, are the predominant immune cells at potential CMV entry sites. Here we show that, upon CMV infection, macrophages undergo a morphological, immunophenotypic, and metabolic transformation process with features of stemness, altered migration, enhanced invasiveness, and provision of the cell cycle machinery for viral proliferation. This complex process depends on Wnt signaling and the transcription factor ZEB1. In pulmonary infection, mouse CMV primarily targets and reprograms alveolar macrophages, which alters lung physiology and facilitates primary CMV and secondary bacterial infection by attenuating the inflammatory response. Thus, CMV profoundly perturbs macrophage identity beyond established limits of plasticity and rewires specific differentiation processes, allowing viral spread and impairing innate tissue immunity.
Topics: Animals; Antigen Presentation; Bystander Effect; Cell Cycle; Cell Line, Transformed; Cellular Reprogramming; Cytomegalovirus; Cytomegalovirus Infections; Green Fluorescent Proteins; Lung; Macrophages, Alveolar; Mice, Inbred BALB C; Mice, Inbred C57BL; Phenotype; Stem Cells; Virus Replication; Wnt Signaling Pathway; Mice
PubMed: 34115982
DOI: 10.1016/j.cell.2021.05.009 -
Frontiers in Immunology 2023Respiratory disorders caused by allergy have been associated to bronchiolar inflammation leading to life-threatening airway narrowing. However, whether airway allergy...
Respiratory disorders caused by allergy have been associated to bronchiolar inflammation leading to life-threatening airway narrowing. However, whether airway allergy causes alveolar dysfunction contributing to the pathology of allergic asthma remains unaddressed. To explore whether airway allergy causes alveolar dysfunction that might contribute to the pathology of allergic asthma, alveolar structural and functional alterations were analyzed during house dust mite (HDM)-induced airway allergy in mice, by flow cytometry, light and electron microscopy, monocyte transfer experiments, assessment of intra-alveolarly-located cells, analysis of alveolar macrophage regeneration in : chimeras, analysis of surfactant-associated proteins, and study of lung surfactant biophysical properties by captive bubble surfactometry. Our results demonstrate that HDM-induced airway allergic reactions caused severe alveolar dysfunction, leading to alveolar macrophage death, pneumocyte hypertrophy and surfactant dysfunction. SP-B/C proteins were reduced in allergic lung surfactant, that displayed a reduced efficiency to form surface-active films, increasing the risk of atelectasis. Original alveolar macrophages were replaced by monocyte-derived alveolar macrophages, that persisted at least two months after the resolution of allergy. Monocyte to alveolar macrophage transition occurred through an intermediate stage of pre-alveolar macrophage and was paralleled with translocation into the alveolar space, Siglec-F upregulation, and downregulation of CX3CR1. These data support that the severe respiratory disorders caused by asthmatic reactions not only result from bronchiolar inflammation, but additionally from alveolar dysfunction compromising an efficient gas exchange.
Topics: Mice; Animals; Macrophages, Alveolar; Hypersensitivity; Asthma; Inflammation; Pulmonary Surfactants; Surface-Active Agents
PubMed: 37234176
DOI: 10.3389/fimmu.2023.1125984 -
The Journal of Clinical Investigation Feb 2021Alveolar macrophages orchestrate the response to viral infections. Age-related changes in these cells may underlie the differential severity of pneumonia in older...
Alveolar macrophages orchestrate the response to viral infections. Age-related changes in these cells may underlie the differential severity of pneumonia in older patients. We performed an integrated analysis of single-cell RNA-Seq data that revealed homogenous age-related changes in the alveolar macrophage transcriptome in humans and mice. Using genetic lineage tracing with sequential injury, heterochronic adoptive transfer, and parabiosis, we found that the lung microenvironment drove an age-related resistance of alveolar macrophages to proliferation that persisted during influenza A viral infection. Ligand-receptor pair analysis localized these changes to the extracellular matrix, where hyaluronan was increased in aged animals and altered the proliferative response of bone marrow-derived macrophages to granulocyte macrophage colony-stimulating factor (GM-CSF). Our findings suggest that strategies targeting the aging lung microenvironment will be necessary to restore alveolar macrophage function in aging.
Topics: Aging; Animals; Cellular Microenvironment; Humans; Lung; Macrophages, Alveolar; Mice; Mice, Transgenic; RNA-Seq
PubMed: 33586677
DOI: 10.1172/JCI140299 -
Immunity Apr 2006Although alveolar macrophages are normally quiescent to prevent damaging the alveoli, in this issue of Immunity, Takabayshi et al. (2006) demonstrate that alveolar... (Review)
Review
Although alveolar macrophages are normally quiescent to prevent damaging the alveoli, in this issue of Immunity, Takabayshi et al. (2006) demonstrate that alveolar macrophages can self-regulate their function on demand to mount an appropriate immune response.
Topics: Animals; Cell Communication; Humans; Macrophage Activation; Macrophages, Alveolar; Pulmonary Alveoli; Respiratory Mucosa
PubMed: 16618595
DOI: 10.1016/j.immuni.2006.03.008 -
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 -
Frontiers in Immunology 2020That macrophages adapt to environmental cues is well-established. This adaptation has had several reiterations, first with innate imprinting and then with various... (Review)
Review
That macrophages adapt to environmental cues is well-established. This adaptation has had several reiterations, first with innate imprinting and then with various combinations of trained, tolerant, paralyzed, or primed. Whatever the nomenclature, it represents a macrophage that is required to perform very different functions. First, alveolar macrophages are one of the sentinel cells that flag up damage and release mediators that attract other immune cells. Next, they mature to support T cell priming and survival. Finally they are critical in clearing inflammatory immune cells by phagocytosis and extracellular matrix turnover components by efferocytosis. At each functional stage they alter intrinsic components to guide their activity. Training therefore is akin to changing function. In this mini-review we focus on the lung and the specific role of type I interferons in altering macrophage activity. The proposed mechanisms of type I IFNs on lung-resident alveolar macrophages and their effect on host susceptibility to bacterial infection following influenza virus infection.
Topics: Adaptive Immunity; Animals; Disease Susceptibility; Epigenome; Humans; Immune Tolerance; Interferon Type I; Macrophage Activation; Macrophages, Alveolar; Pneumonia, Bacterial
PubMed: 32265937
DOI: 10.3389/fimmu.2020.00495