Skip to main content
construction release_alert
Scholars@Duke will be undergoing maintenance April 11-15. Some features may be unavailable during this time.
cancel

Nonclassical Monocytes Sense Hypoxia, Regulate Pulmonary Vascular Remodeling, and Promote Pulmonary Hypertension.

Publication ,  Journal Article
Yu, Y-RA; Malakhau, Y; Yu, C-HA; Phelan, S-LJ; Cumming, RI; Kan, MJ; Mao, L; Rajagopal, S; Piantadosi, CA; Gunn, MD
Published in: J Immunol
March 15, 2020

An increasing body of evidence suggests that bone marrow-derived myeloid cells play a critical role in the pathophysiology of pulmonary hypertension (PH). However, the true requirement for myeloid cells in PH development has not been demonstrated, and a specific disease-promoting myeloid cell population has not been identified. Using bone marrow chimeras, lineage labeling, and proliferation studies, we determined that, in murine hypoxia-induced PH, Ly6Clo nonclassical monocytes are recruited to small pulmonary arteries and differentiate into pulmonary interstitial macrophages. Accumulation of these nonclassical monocyte-derived pulmonary interstitial macrophages around pulmonary vasculature is associated with increased muscularization of small pulmonary arteries and disease severity. To determine if the sensing of hypoxia by nonclassical monocytes contributes to the development of PH, mice lacking expression of hypoxia-inducible factor-1α in the Ly6Clo monocyte lineage were exposed to hypoxia. In these mice, vascular remodeling and PH severity were significantly reduced. Transcriptome analyses suggest that the Ly6Clo monocyte lineage regulates PH through complement, phagocytosis, Ag presentation, and chemokine/cytokine pathways. Consistent with these murine findings, relative to controls, lungs from pulmonary arterial hypertension patients displayed a significant increase in the frequency of nonclassical monocytes. Taken together, these findings show that, in response to hypoxia, nonclassical monocytes in the lung sense hypoxia, infiltrate small pulmonary arteries, and promote vascular remodeling and development of PH. Our results demonstrate that myeloid cells, specifically cells of the nonclassical monocyte lineage, play a direct role in the pathogenesis of PH.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

J Immunol

DOI

EISSN

1550-6606

Publication Date

March 15, 2020

Volume

204

Issue

6

Start / End Page

1474 / 1485

Location

United States

Related Subject Headings

  • Vascular Remodeling
  • Transplantation Chimera
  • Pulmonary Artery
  • Monocytes
  • Mice, Transgenic
  • Mice
  • Male
  • Macrophages, Alveolar
  • Lung Transplantation
  • Lung
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Yu, Y.-R., Malakhau, Y., Yu, C.-H., Phelan, S.-L., Cumming, R. I., Kan, M. J., … Gunn, M. D. (2020). Nonclassical Monocytes Sense Hypoxia, Regulate Pulmonary Vascular Remodeling, and Promote Pulmonary Hypertension. J Immunol, 204(6), 1474–1485. https://doi.org/10.4049/jimmunol.1900239
Yu, Yen-Rei A., Yuryi Malakhau, Chen-Hsin A. Yu, Stefan-Laural J. Phelan, R Ian Cumming, Matthew J. Kan, Lan Mao, Sudarshan Rajagopal, Claude A. Piantadosi, and Michael D. Gunn. “Nonclassical Monocytes Sense Hypoxia, Regulate Pulmonary Vascular Remodeling, and Promote Pulmonary Hypertension.J Immunol 204, no. 6 (March 15, 2020): 1474–85. https://doi.org/10.4049/jimmunol.1900239.
Yu Y-RA, Malakhau Y, Yu C-HA, Phelan S-LJ, Cumming RI, Kan MJ, et al. Nonclassical Monocytes Sense Hypoxia, Regulate Pulmonary Vascular Remodeling, and Promote Pulmonary Hypertension. J Immunol. 2020 Mar 15;204(6):1474–85.
Yu, Yen-Rei A., et al. “Nonclassical Monocytes Sense Hypoxia, Regulate Pulmonary Vascular Remodeling, and Promote Pulmonary Hypertension.J Immunol, vol. 204, no. 6, Mar. 2020, pp. 1474–85. Pubmed, doi:10.4049/jimmunol.1900239.
Yu Y-RA, Malakhau Y, Yu C-HA, Phelan S-LJ, Cumming RI, Kan MJ, Mao L, Rajagopal S, Piantadosi CA, Gunn MD. Nonclassical Monocytes Sense Hypoxia, Regulate Pulmonary Vascular Remodeling, and Promote Pulmonary Hypertension. J Immunol. 2020 Mar 15;204(6):1474–1485.

Published In

J Immunol

DOI

EISSN

1550-6606

Publication Date

March 15, 2020

Volume

204

Issue

6

Start / End Page

1474 / 1485

Location

United States

Related Subject Headings

  • Vascular Remodeling
  • Transplantation Chimera
  • Pulmonary Artery
  • Monocytes
  • Mice, Transgenic
  • Mice
  • Male
  • Macrophages, Alveolar
  • Lung Transplantation
  • Lung