The Effects of Pulmonary Atelectasis and Reexpansion on Lung Cellular Immune Defenses

Shennib, Hani; Mulder, David S.; Chiu, Ray Chu‐Jeng

doi:10.1001/archsurg.1984.01390150016004

Cited by 17 publications

(9 citation statements)

References 24 publications

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“…They are also consistent with previous findings of impaired alveolar macrophage function 15 and less regional lung injury 30,31 in atelectasis. However, they contrast with reports of atelectasis association with a proinflammatory state in rats 11,12 .…”

Section: Discussionsupporting

confidence: 92%

“…A few reports have shown increased inflammatory activity with neutrophil infiltration and potentiation of the neutrophil oxidative response in atelectatic lung 11,12 . In contrast, others found no increase in neutrophil recruitment and inflammatory cytokine production 13,14 or even an inflammatory dysfunction for alveolar macrophages 15 . In vitro studies suggest that pulmonary endothelial cell immobility, as present in atelectatic tissue, impaired pulmonary barrier recovery ability and increased lung permeability in response to thrombin 16 .…”

Section: Introductionmentioning

confidence: 94%

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Lung Atelectasis Promotes Immune and Barrier Dysfunction as Revealed by Transcriptome Sequencing in Female Sheep

Zeng¹,

Ribeiro²,

Hinoshita³

et al. 2020

Anesthesiology

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Background Pulmonary atelectasis is frequent in clinical settings. Yet there is limited mechanistic understanding and substantial clinical and biologic controversy on its consequences. The authors hypothesize that atelectasis produces local transcriptomic changes related to immunity and alveolar–capillary barrier function conducive to lung injury and further exacerbated by systemic inflammation. Methods Female sheep underwent unilateral lung atelectasis using a left bronchial blocker and thoracotomy while the right lung was ventilated, with (n = 6) or without (n = 6) systemic lipopolysaccharide infusion. Computed tomography guided samples were harvested for NextGen RNA sequencing from atelectatic and aerated lung regions. The Wald test was used to detect differential gene expression as an absolute fold change greater than 1.5 and adjusted P value (Benjamini–Hochberg) less than 0.05. Functional analysis was performed by gene set enrichment analysis. Results Lipopolysaccharide-unexposed atelectatic versus aerated regions presented 2,363 differentially expressed genes. Lipopolysaccharide exposure induced 3,767 differentially expressed genes in atelectatic lungs but only 1,197 genes in aerated lungs relative to the corresponding lipopolysaccharide-unexposed tissues. Gene set enrichment for immune response in atelectasis versus aerated tissues yielded negative normalized enrichment scores without lipopolysaccharide (less than –1.23, adjusted P value less than 0.05) but positive scores with lipopolysaccharide (greater than 1.33, adjusted P value less than 0.05). Leukocyte-related processes (e.g., leukocyte migration, activation, and mediated immunity) were enhanced in lipopolysaccharide-exposed atelectasis partly through interferon-stimulated genes. Furthermore, atelectasis was associated with negatively enriched gene sets involving alveolar–capillary barrier function irrespective of lipopolysaccharide (normalized enrichment scores less than –1.35, adjusted P value less than 0.05). Yes-associated protein signaling was dysregulated with lower nuclear distribution in atelectatic versus aerated lung (lipopolysaccharide-unexposed: 10.0 ± 4.2 versus 13.4 ± 4.2 arbitrary units, lipopolysaccharide-exposed: 8.1 ± 2.0 versus 11.3 ± 2.4 arbitrary units, effect of lung aeration, P = 0.003). Conclusions Atelectasis dysregulates the local pulmonary transcriptome with negatively enriched immune response and alveolar–capillary barrier function. Systemic lipopolysaccharide converts the transcriptomic immune response into positive enrichment but does not affect local barrier function transcriptomics. Interferon-stimulated genes and Yes-associated protein might be novel candidate targets for atelectasis-associated injury. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 94%

Lung Atelectasis Promotes Immune and Barrier Dysfunction as Revealed by Transcriptome Sequencing in Female Sheep

Zeng¹,

Ribeiro²,

Hinoshita³

et al. 2020

Anesthesiology

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“…We can only speculate on the reasons why a reduction in atelectasis mitigated bacterial growth in the lung. First, Shennib and colleagues showed that the in vitro function of AMs can be impaired if the lung is subjected to several hours of atelectasis (27).…”

Section: Discussionmentioning

confidence: 99%

Reducing Atelectasis Attenuates Bacterial Growth and Translocation in Experimental Pneumonia

Kaam

Lachmann

Herting

et al. 2004

Am J Respir Crit Care Med

201

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Besides being one of the mechanisms responsible for ventilator-induced lung injury, atelectasis also seems to aggravate the course of experimental pneumonia. In this study, we examined the effect of reducing the degree of atelectasis by natural modified surfactant and/or open lung ventilation on bacterial growth and translocation in a piglet model of Group B streptococcal pneumonia. After creating surfactant deficiency by whole lung lavage, intratracheal instillation of bacteria induced severe pneumonia with bacterial translocation into the blood stream, resulting in a mortality rate of almost 80%. Treatment with 300 mg/kg of exogenous surfactant before instillation of streptococci attenuated both bacterial growth and translocation and prevented clinical deterioration. This goal was also achieved by reversing atelectasis in lavaged animals via open lung ventilation. Combining both exogenous surfactant and open lung ventilation prevented bacterial translocation completely, comparable to Group B streptococci instillation into healthy animals. We conclude that exogenous surfactant and open lung ventilation attenuate bacterial growth and translocation in experimental pneumonia and that this attenuation is at least in part mediated by a reduction in atelectasis. These findings suggest that minimizing alveolar collapse by exogenous surfactant and open lung ventilation may reduce the risk of pneumonia and subsequent sepsis in ventilated patients.

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“…Studies addressing cellular immune function and cytokine production in atelectatic lung have reported conflicting enhanced 5 , 8 and impaired 9 , 10 responses. During atelectasis, the increased inflammatory responses included activation of alveolar macrophages and neutrophils with cytokine release 11 , 12 ; and the infiltration of neutrophils in atelectatic or peri-atelectatic regions 12 , 13 .…”

Section: Introductionmentioning

confidence: 99%

Proteomics of lung tissue reveals differences in inflammation and alveolar-capillary barrier response between atelectasis and aerated regions

Rashid

Zeng

Ribeiro

et al. 2022

Sci Rep

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Atelectasis is a frequent clinical condition, yet knowledge is limited and controversial on its biological contribution towards lung injury. We assessed the regional proteomics of atelectatic versus normally-aerated lung tissue to test the hypothesis that immune and alveolar-capillary barrier functions are compromised by purely atelectasis and dysregulated by additional systemic inflammation (lipopolysaccharide, LPS). Without LPS, 130 proteins were differentially abundant in atelectasis versus aerated lung, mostly (n = 126) with less abundance together with negatively enriched processes in immune, endothelial and epithelial function, and Hippo signaling pathway. Instead, LPS-exposed atelectasis produced 174 differentially abundant proteins, mostly (n = 108) increased including acute lung injury marker RAGE and chemokine CCL5. Functional analysis indicated enhanced leukocyte processes and negatively enriched cell–matrix adhesion and cell junction assembly with LPS. Additionally, extracellular matrix organization and TGF-β signaling were negatively enriched in atelectasis with decreased adhesive glycoprotein THBS1 regardless of LPS. Concordance of a subset of transcriptomics and proteomics revealed overlap of leukocyte-related gene-protein pairs and processes. Together, proteomics of exclusively atelectasis indicates decreased immune response, which converts into an increased response with LPS. Alveolar-capillary barrier function-related proteomics response is down-regulated in atelectasis irrespective of LPS. Specific proteomics signatures suggest biological mechanistic and therapeutic targets for atelectasis-associated lung injury.

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The Effects of Pulmonary Atelectasis and Reexpansion on Lung Cellular Immune Defenses

Cited by 17 publications

References 24 publications

Lung Atelectasis Promotes Immune and Barrier Dysfunction as Revealed by Transcriptome Sequencing in Female Sheep

Lung Atelectasis Promotes Immune and Barrier Dysfunction as Revealed by Transcriptome Sequencing in Female Sheep

Reducing Atelectasis Attenuates Bacterial Growth and Translocation in Experimental Pneumonia

Proteomics of lung tissue reveals differences in inflammation and alveolar-capillary barrier response between atelectasis and aerated regions

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