Alveolar macrophages have a dual role in a rat model for trimellitic anhydride-induced occupational asthma

Valstar, Dingena L.; Schijf, Marcel A.; Nijkamp, Frans P.; Storm, Gert; Arts, J.H.E.; Kuper, C. Frieke; Bloksma, N.; Henricks, Paul A.J.

doi:10.1016/j.taap.2005.05.012

Cited by 15 publications

(12 citation statements)

References 32 publications

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“…Similar findings were observed, in a rat model of trimellitic anhydride-induced occupational asthma (Valstar et al, 2006). The authors reported that AM depletion augmented the trimellitic anhydride-induced tissue damage and inflammation 24 h after challenge.…”

Section: Discussionsupporting

confidence: 81%

Alveolar macrophages modulate allergic inflammation in a murine model of asthma

et al. 2011

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The role of alveolar macrophages (AMs) in the pathogenesis of asthma is still unknown. The aim of the present study was to investigate the effects of AM in the murine model of asthma. AMs were selectively depleted by liposomes containing clodronate just before allergen challenges, and changes in inflammatory cells and cytokine concentrations in bronchoalveolar lavage (BAL) fluid were measured. AMs were then adoptively transferred to AM-depleted sensitized mice and changes were measured. Phenotypic changes in AMs were evaluated after in vitro allergen stimulation. AM-depletion after sensitization significantly increased the number of eosinophils and lymphocytes and the concentrations of IL-4, IL-5 and GM-CSF in BAL fluid. These changes were significantly ameliorated only by adoptive transfer of unsensitized AMs, not by sensitized AMs. In addition, in vitro allergen stimulation of AMs resulted in their gaining the ability to produce inflammatory cytokines, such as IL-1β, IL-6 and TNF-α, and losing the ability to suppress GM-CSF concentrations in BAL fluid. These findings suggested that AMs worked probably through GM-CSF-dependent mechanisms, although further confirmatory experiments are needed. Our results indicate that the role of AMs in the context of airway inflammation should be re-examined.

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Section: Discussionsupporting

confidence: 81%

Alveolar macrophages modulate allergic inflammation in a murine model of asthma

et al. 2011

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“…After Cl 2 exposure, we measured respiratory system mechanics in response to inhaled methacholine (MCh) and assessed airway inflammatory cell profiles, proinflammatory cytokine levels, antioxidant gene expression, and nuclear factor (erythroid-derived 2)-like 2 (NRF-2) epithelial cell nuclear translocation in vivo and in vitro. We also assessed the independent contribution of eosinophils and macrophages in the induction of Cl 2 -induced AHR and inflammation using an anti-IL-5 antibody (30) or intratracheal and systemic administration of clodronate liposomes (31)(32)(33), respectively.…”

Section: Clinical Relevancementioning

confidence: 99%

Neutrophils Mediate Airway Hyperresponsiveness after Chlorine-Induced Airway Injury in the Mouse

McGovern

Goldberger²,

Allard³

et al. 2015

Am J Respir Cell Mol Biol

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Chlorine gas (Cl2) inhalation causes oxidative stress, airway epithelial damage, airway hyperresponsiveness (AHR), and neutrophilia. We evaluated the effect of neutrophil depletion on Cl2-induced AHR and its effect on the endogenous antioxidant response, and if eosinophils or macrophages influence Cl2-induced AHR. We exposed male Balb/C mice to 100 ppm Cl2 for 5 minutes. We quantified inflammatory cell populations in bronchoalveolar lavage (BAL), the antioxidant response in lung tissue by quantitative PCR, and nuclear factor (erythroid-derived 2)-like 2 (NRF2) nuclear translocation by immunofluorescence. In vitro, NRF2 nuclear translocation in response to exogenous hypochlorite was assessed using a luciferase assay. Anti-granulocyte receptor-1 antibody or anti-Ly6G was used to deplete neutrophils. The effects of neutrophil depletion on IL-13 and IL-17 were measured by ELISA. Eosinophils and macrophages were depleted using TRFK5 or clodronate-loaded liposomes, respectively. AHR was evaluated with the constant-phase model in response to inhaled aerosolized methacholine. Our results show that Cl2 exposure induced neutrophilia and increased expression of NRF2 mRNA, superoxide dismutase-1, and heme-oxygenase 1. Neutrophil depletion abolished Cl2-induced AHR in large conducting airways and prevented increases in antioxidant gene expression and NRF2 nuclear translocation. Exogenous hypochlorite administration resulted in increased NRF2 nuclear translocation in vitro. After Cl2 exposure, neutrophils occupied 22 ± 7% of the luminal space in large airways. IL-17 in BAL was increased after Cl2, although this effect was not prevented by neutrophil depletion. Neither depletion of eosinophils nor macrophages prevented Cl2-induced AHR. Our data suggest the ability of neutrophils to promote Cl2-induced AHR is dependent on increases in oxidative stress and occupation of luminal space in large airways.

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“…AM directly contribute to surfactant metabolism and are thought to be crucially involved in the generation of acute as well as chronic allergic reactions of the respiratory tract. In this context, the biology of AM has been extensively studied and both protective as well as detrimental functions of AM could be elucidated in different models of asthma and allergic airway diseases [7,8,9,10,11,12,13,14,15]. Previous studies have suggested that AM may also play a role in the development of secondary pulmonary disorders like acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) [16, 17].…”

Section: Introductionmentioning

confidence: 99%

Selective Depletion of Alveolar Macrophages in Polymicrobial Sepsis Increases Lung Injury, Bacterial Load and Mortality but Does Not Affect Cytokine Release

et al. 2008

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Background: Resident tissue macrophages exert important functions during severe systemic infection and contribute to changes in local as well as systemic immune responses. Alveolar macrophages (AM) play a crucial role in airway diseases and in the defense against microorganisms invading the body via the bronchopulmonary tract. It has been postulated that AM are involved in the development of acute local disorders as a consequence of extrapulmonary stimuli like pancreatitis, peritonitis, or trauma. Objective: The aim of this study was to analyze the local and systemic role of AM during sepsis using selective AM depletion in the murine colon ascendens stent peritonitis (CASP) model of polymicrobial sepsis. Methods: 48 h prior to CASP surgery, AM of female C57BL/6 mice were selectively depleted by intratracheal application of clodronate liposomes (Lipo-clod). For control purposes, phosphate-buffered saline (PBS) liposomes (Lipo-PBS) were used. Results: CASP led to significantly elevated levels of local and systemic cytokines independent of the presence of AM. In contrast, levels of gut-derived bacteria in bronchoalveolar lavage and lung of septic mice were significantly higher in Lipo-clod-treated animals compared to Lipo-PBS-treated animals. After CASP-induced sepsis, local barrier dysfunction in the lung was detected; AM depletion resulted in severely enhanced development of acute lung injury. Consequently, Lipo-clod-treated animals showed strongly reduced survival rates after CASP. Conclusions: Contrarily to other macrophage populations, AM do not significantly contribute to local and systemic cytokine release during polymicrobial abdominal sepsis. AM have important protective functions for local clearance of gut-derived bacteria and attenuation of lung injury.

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Alveolar macrophages have a dual role in a rat model for trimellitic anhydride-induced occupational asthma

Cited by 15 publications

References 32 publications

Alveolar macrophages modulate allergic inflammation in a murine model of asthma

Alveolar macrophages modulate allergic inflammation in a murine model of asthma

Neutrophils Mediate Airway Hyperresponsiveness after Chlorine-Induced Airway Injury in the Mouse

Selective Depletion of Alveolar Macrophages in Polymicrobial Sepsis Increases Lung Injury, Bacterial Load and Mortality but Does Not Affect Cytokine Release

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