You are here:
Macrophages from Upper and Lower Human Respiratory Tract are Metabolically Distinct
Citation:
Ghio, Andy, K. Lavrich, J. Samet, P. Bromberg, N. Alexis, AND A. Speen. Macrophages from Upper and Lower Human Respiratory Tract are Metabolically Distinct. American Journal of Physiology - Lung Cellular and Molecular Physiology. American Physiological Society, Bethesda, MD, 315(5):L752-L764, (2018). https://doi.org/10.1152/ajplung.00208.2018
Impact/Purpose:
This manuscript reports research findings from a study that characterized the bioenergetic profiles of immune cells recovered from different compartments in the human lung. It shows distinct subpopulations of immune cells in the upper and lower respiratory tract, suggesting differential susceptibility to inhalational exposure of air pollutants at these anatomical locations within the lung.
Description:
Rationale The function and phenotype of lung macrophages varies within the respiratory tract. Whether the bioenergetic profile of macrophages correlates with their location within the lung is currently unknown. Objectives 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. Methods Macrophages recovered from healthy volunteers by induced sputum or by either bronchial or bronchoalveolar lavage were profiled using extracellular flux analyses. Oxygen consumption and extracellular acidification rates were measured at rest and after stimulation with lipopolysaccharide, phorbol 12-myristate 13-acetate, or the air pollutant 1,2-naphthoquinone. Measurements and Main Results 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, bronchoalveolar and bronchial fraction macrophages depended more heavily on mitochondrial respiration. Bronchoalveolar macrophages showed elevated lipopolysaccharide-induced cytokine responses. Unlike their autologous peripheral monocytes, lung macrophages from any sample type did not display the expected increase in extracellular acidification rate following lipopolysaccharide stimulation, despite demonstrating cytokine responses. Phorbol 12-myristate 13-acetate did not affect mitochondrial respiration, while 10 uM 1,2-naphthoquinone induced marked mitochondrial dysfunction in bronchoalveolar and bronchial fraction macrophages. Conclusions The bioenergetic characteristics of macrophages from healthy individuals are dependent on their location within the respiratory tract. These findings will establish a regional bioenergetic profile for macrophages from healthy human airways that serves as a reference for changes that occur in disease.
URLs/Downloads:
DOI: Macrophages from Upper and Lower Human Respiratory Tract are Metabolically Distinct