Mitochondrial respiratory dysfunctions of alveolar macrophages in interstitial lung disease: an exploratory study of bioenergetic and clinical links

TL;DR

This study explores how mitochondrial function in lung macrophages differs between patients with and without interstitial lung disease, suggesting a potential link to disease progression.

Contribution

The study identifies mitochondrial bioenergetic dysfunction in alveolar macrophages from interstitial lung disease patients as a novel potential biomarker.

Findings

ILD patients had significantly reduced ATP-linked respiration in alveolar macrophages compared to non-ILD patients.

Principal component analysis and logistic regression successfully distinguished ILD from non-ILD cases based on bioenergetic metrics.

ATP-linked respiration and coupling efficiency were independent predictors of ILD status.

Abstract

Intracellular metabolism is essential for macrophage function. However, the association between the metabolic profile of alveolar macrophages (AMs), which are responsible for pulmonary innate immune responses, and the progression of pulmonary fibrosis in humans remains unclear.

This exploratory study investigated whether mitochondrial bioenergetics in bronchoalveolar lavage (BAL)-derived AMs can distinguish interstitial lung disease (ILD) from non-ILD conditions. A total of 12 patients undergoing diagnostic BAL were analyzed (ILD, n = 7; non-ILD, n = 5). CD11c+ AMs were isolated and analyzed using an extracellular flux analyzer to quantify metabolic parameters. Principal component analysis (PCA) and penalized logistic regression were used for multivariate discrimination.

The AMs in ILD showed reduced ATP-linked respiration (3.55 vs. 10.67 pmol/min/105 cells, p = 0.003) and coupling efficiency (10.55% vs. 25.81%, p = 0.018) compared with non-ILD AMs. PCA using all four metrics distinguished ILD from non-ILD AMs. Logistic regression classified subjects with 83% cross-validated accuracy. ATP-linked respiration and coupling efficiency were independent predictors under Firth correction. Collectively, AMs from ILD cases exhibited mitochondrial dysfunction, particularly reduced ATP-linked respiration.

This bioenergetic profile may offer preliminary insights into mitochondrial bioenergetic alterations in AMs from ILDs and their potential relevance to disease characterization. Larger longitudinal studies are warranted to validate these findings and their clinical utility.

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