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The transcriptional and phenotypic characteristics that define alveolar macrophage subsets in acute hypoxemic respiratory failure

Author

Listed:
  • Eric D. Morrell

    (University of Washington)

  • Sarah E. Holton

    (University of Washington)

  • Matthew Lawrance

    (Benaroya Research Institute)

  • Marika Orlov

    (University of Colorado)

  • Zoie Franklin

    (Benaroya Research Institute)

  • Mallorie A. Mitchem

    (Benaroya Research Institute)

  • Hannah DeBerg

    (Benaroya Research Institute)

  • Vivian H. Gersuk

    (Benaroya Research Institute)

  • Ashley Garay

    (University of Washington)

  • Elizabeth Barnes

    (University of Washington)

  • Ted Liu

    (University of Washington)

  • Ithan D. Peltan

    (Intermountain Health)

  • Angela Rogers

    (Stanford University)

  • Steven Ziegler

    (Benaroya Research Institute)

  • Mark M. Wurfel

    (University of Washington)

  • Carmen Mikacenic

    (Benaroya Research Institute)

Abstract

The transcriptional and phenotypic characteristics that define alveolar monocyte and macrophage subsets in acute hypoxemic respiratory failure (AHRF) are poorly understood. Here, we apply CITE-seq (single-cell RNA-sequencing and cell-surface protein quantification) to bronchoalveolar lavage and blood specimens longitudinally collected from participants with AHRF to identify alveolar myeloid subsets, and then validate their identity in an external cohort using flow cytometry. We identify alveolar myeloid subsets with transcriptional profiles that differ from other lung diseases as well as several subsets with similar transcriptional profiles as reported in healthy participants (Metallothionein) or patients with COVID-19 (CD163/LGMN). We use information from CITE-seq to determine cell-surface proteins that distinguish transcriptional subsets (CD14, CD163, CD123, CD71, CD48, CD86 and CD44). In the external cohort, we find a higher proportion of CD163/LGMN alveolar macrophages are associated with mortality in AHRF. We report a parsimonious set of cell-surface proteins that distinguish alveolar myeloid subsets using scalable approaches that can be applied to clinical cohorts.

Suggested Citation

  • Eric D. Morrell & Sarah E. Holton & Matthew Lawrance & Marika Orlov & Zoie Franklin & Mallorie A. Mitchem & Hannah DeBerg & Vivian H. Gersuk & Ashley Garay & Elizabeth Barnes & Ted Liu & Ithan D. Pelt, 2023. "The transcriptional and phenotypic characteristics that define alveolar macrophage subsets in acute hypoxemic respiratory failure," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-43223-0
    DOI: 10.1038/s41467-023-43223-0
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