A Time- and Compartment-Specific Activation of Lung Macrophages in Hypoxic Pulmonary Hypertension

The Journal of Immunology : Official Journal of the American Association of Immunologists
Steven C PuglieseKurt R Stenmark

Abstract

Studies in various animal models suggest an important role for pulmonary macrophages in the pathogenesis of pulmonary hypertension (PH). Yet, the molecular mechanisms characterizing the functional macrophage phenotype relative to time and pulmonary localization and compartmentalization remain largely unknown. In this study, we used a hypoxic murine model of PH in combination with FACS to quantify and isolate lung macrophages from two compartments over time and characterize their programing via RNA sequencing approaches. In response to hypoxia, we found an early increase in macrophage number that was restricted to the interstitial/perivascular compartment, without recruitment of macrophages to the alveolar compartment or changes in the number of resident alveolar macrophages. Principal component analysis demonstrated significant differences in overall gene expression between alveolar and interstitial macrophages (IMs) at baseline and after 4 and 14 d hypoxic exposure. Alveolar macrophages at both day 4 and 14 and IMs at day 4 shared a conserved hypoxia program characterized by mitochondrial dysfunction, proinflammatory gene activation, and mTORC1 signaling, whereas IMs at day 14 demonstrated a unique anti-inflammatory/proreparat...Continue Reading

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Feb 27, 2018·Pulmonary Circulation·Isaac P Pinar, Heather D Jones
Apr 11, 2018·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jonathan FlorentinPartha Dutta
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Apr 2, 2021·Frontiers in Cardiovascular Medicine·Haihua QiuYuan Guo

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