Cytometry TOF identifies alveolar macrophage subtypes in acute respiratory distress syndrome

JCI Insight
Eric D MorrellCarmen Mikacenic

Abstract

Studies in human peripheral blood monocyte-derived macrophages in vitro have shown clear evidence that multiple macrophage polarization states exist. The extent to which different alveolar macrophage (AM) polarization states exist in homeostasis or in the setting of severe injury such as acute respiratory distress syndrome (ARDS) is largely unknown. We applied single-cell cytometry TOF (CyTOF) to simultaneously measure 36 cell-surface markers on CD45+ cells present in bronchoalveolar lavage from healthy volunteers, as well as mechanically ventilated subjects with and without ARDS. Visualization of the high-dimensional data with the t-distributed stochastic neighbor embedding algorithm demonstrated wide diversity of cell-surface marker profiles among CD33+CD71+CD163+ AMs. We then used a κ-nearest neighbor density estimation algorithm to statistically identify distinct alveolar myeloid subtypes, and we discerned 3 AM subtypes defined by CD169 and PD-L1 surface expression. The percentage of AMs that were classified into one of the 3 AM subtypes was significantly different between healthy and mechanically ventilated subjects. In an independent cohort of subjects with ARDS, PD-L1 gene expression and PD-L1/PD-1 pathway-associated gen...Continue Reading

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Citations

Jul 31, 2019·The Journal of Clinical Investigation·Simon P JochemsDaniela M Ferreira
Jul 18, 2019·American Journal of Respiratory and Critical Care Medicine·Eric D MorrellSina A Gharib
Feb 6, 2020·Pediatric Pulmonology·Judith Ju-Ming WongJan Hau Lee
Apr 17, 2019·American Journal of Respiratory and Critical Care Medicine·Eric D MorrellSina A Gharib
May 5, 2020·Hepatology Communications·Omar A SaldarriagaHeather L Stevenson
May 21, 2019·American Journal of Respiratory and Critical Care Medicine·Vickram Tejwani, Franco R D'Alessio
Jul 17, 2019·Therapeutic Advances in Infectious Disease·Jack Varon, Rebecca M Baron
Dec 28, 2018·Critical Care : the Official Journal of the Critical Care Forum·Carmen MikacenicChristian Lood
Sep 16, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Charles Preston NeffBrent E Palmer
Oct 7, 2020·The Journal of Clinical Investigation·Franco R D'Alessio, Nicola M Heller
Nov 1, 2020·Cell Death & Disease·Jing XuJialin Liu
Sep 12, 2020·American Journal of Respiratory Cell and Molecular Biology·Sreelakshmi VasudevanMehrdad Arjomandi
Sep 13, 2018·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Giuseppe Lo RussoMarina Chiara Garassino
Jan 8, 2021·Critical Care : the Official Journal of the Critical Care Forum·Marika OrlovCarmen Mikacenic
Jan 11, 2021·Critical Care : the Official Journal of the Critical Care Forum·Inès BendibNicolas de Prost

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Methods Mentioned

BETA
flow cytometry
flow
bronchoalveolar lavage
lavage
flow cytometry gating
sedation
electrophoresis
chip
blood draw

Software Mentioned

κNN
GraphPad
GraphPad Prism
DE Tree
Gene Set Enrichment Analysis ( GSEA
GSEA
Cytobank Premium
AMGE
CyTOF
Shift

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