Macrophages from the upper and lower human respiratory tract are metabolically distinct

Abstract

The function and cell surface phenotype of lung macrophages vary within the respiratory tract. Whether the bioenergetic profile of macrophages also differs depending on location within the lung is currently unknown. This study sought to characterize the bioenergetic profile of macrophages sampled from different locations within the respiratory tract at baseline and in response to ex vivo xenobiotic challenge. Surface macrophages recovered from healthy volunteers by induced sputum and by bronchial and bronchoalveolar lavage were profiled using extracellular flux analyses. Oxygen consumption and extracellular acidification rates were measured at rest and after stimulation with lipopolysaccharide (LPS), phorbol 12-myristate 13-acetate (PMA), or 1,2-naphthoquinone (1,2-NQ). Oxygen consumption and extracellular acidification rates were highly correlated for all macrophage samples. Induced sputum macrophages had relatively higher oxygen consumption and extracellular acidification rates, and were largely reliant on glycolysis. In contrast, bronchial fraction and bronchoalveolar macrophages depended more heavily on mitochondrial respiration. Bronchoalveolar macrophages showed elevated LPS-induced cytokine responses. Unlike their autologous peripheral blood monocytes, lung macrophages from any source did not display bioenergetic changes following LPS stimulation. The protein kinase C activator PMA did not affect mitochondrial respiration, while the air pollutant 1,2-NQ induced marked mitochondrial dysfunction in bronchoalveolar and bronchial fraction macrophages. The bioenergetic characteristics of macrophages from healthy individuals are dependent on their location within the respiratory tract. These findings establish a regional bioenergetic profile for macrophages from healthy human airways that serves as a reference for changes that occur in disease.

Human and murine macrophages exhibit differential metabolic responses to lipopolysaccharide - A divergent role for glycolysis

“…The differences in ΔΨm and resistance to mitochondrial dysfunction that was observed in this study might also be of evolutionary significance and has to be explored further. While we acknowledge the limitation of this study that might arise from the use of hMDMs (which is the most widely used model of human macrophages) in comparison to BMDMs from mouse, our findings are in accordance with a previous observation that human lung macrophages displayed no metabolic alterations upon LPS stimulation in vitro [21]. The increased glycolysis characteristic of mouse macrophages with mitochondrial dysfunction appears to play a role in cell survival as previously shown for astrocytes [22].…”

Common E-Cigarette Flavoring Chemicals Impair Neutrophil Phagocytosis and Oxidative Burst

“…8 However, bioenergetic characterization of the innate immune system has been limited primarily to macrophages, while neutrophils have been largely ignored. 9,10 Furthermore, the ability of toxicants to alter neutrophil bioenergetics and downstream functions remains unclear. Our lab has demonstrated that the flavoring chemical cinnamaldehyde significantly affects cellular bioenergetics, which in turn causes impairment of key innate immune functions of respiratory epithelial cells.…”

Nucleoredoxin Knockdown in SH-SY5Y Cells Promotes Cell Renewal

“…They may increase the respiratory rate or glycolysis to meet the requirements. We therefore assessed mitochondrial respiration, ATP generation, and the balancing of oxygen consumption (OCR, Figure 3 A,B,D) and extracellular acidification rate (ECAR, Figure 3 C,D), key indicators of mitochondrial respiration and glycolysis, respectively [ 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 39 ]. Indeed, absolute basal OCR in the presence of full nutrients and supplements (pyruvate, glutamine and glucose) was much higher in shNXN cultures ( Figure 3 A).…”

“…Mitochondrial respiration and extracellular acidification were analyzed simultaneously on a Seahorse XFp instrument using an XFp “Cell Mito Stress Test” (Agilent Technologies, 76337 Waldbronn, Germany) [ 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 ]. This is a plate-based live cell assay for monitoring of oxygen consumption and extracellular acidification rates in live cells.…”