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

Abstract

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.

Prone Positioning and Molecular Biomarkers in COVID and Non-COVID ARDS: A Narrative Review

“…Evaluating the effect of atelectasis on proteomics is fundamental to understanding the biological alterations generated by ARDS. Rashid et al [98] studied proteomics following a model of acute lung damage generated with lipopolysaccharide (LPS) and endotoxin. They were able to reflect how atelectasis in these cases has a clear effect on increasing inflammation and dysfunction of the alveolar-capillary membrane.…”

“…As markers of alveolar-capillary dysfunction, they found extracellular matrix glycoproteins, vascular endothelial growth factor, and fibrinogen independently of the presence of systemic endotoxemia. Additionally, Endotoxemia promoted further metabolic changes in atelectasis with increased glycolytic enzymes, carbon metabolism, and glycolysis pathways [98].…”

Personalized medicine using omics approaches in acute respiratory distress syndrome to identify biological phenotypes

“…In a recent large animal study, proteomics of lung tissue revealed differences in inflammation and alveolar‑capillary barrier response between atelectasis and aerated regions. Atelectasis regions showed a predominance of negative enrichment related to the extracellular matrix, immune response, tissue development, stress, and metabolism [ 168 ]. In a mice model, Yue et al [ 169 ] observed that the proteomic profile differs between direct lipopolysaccharide-induced lung injury and indirect lung injury.…”