Analysis of lung stromal expression of the atypical chemokine receptor ACKR2 reveals unanticipated expression in murine blood endothelial cells

Eur J Immunol. 2020 May;50(5):666-675. doi: 10.1002/eji.201948374. Epub 2020 Mar 17.

Abstract

Analysis of chemokine receptor, and atypical chemokine receptor, expression is frequently hampered by the lack of availability of high-quality antibodies and the species specificity of those that are available. We have previously described methodology utilizing Alexa-Fluor-labeled chemokine ligands as versatile reagents to detect receptor expression. Previously this has been limited to hematopoietic cells and methodology for assessing expression of receptors on stromal cells has been lacking. Among chemokine receptors, the ones most frequently expressed on stromal cells belong to the atypical chemokine receptor subfamily. These receptors do not signal in the classic sense in response to ligand but scavenge their ligands and degrade them and thus sculpt in vivo chemokine gradients. Here, we demonstrate the ability to use either intratracheal or intravenous, Alexa-Fluor-labeled chemokine administration to detect stromal cell populations expressing the atypical chemokine receptor ACKR2. Using this methodology, we demonstrate, for the first time, expression of ACKR2 on blood endothelial cells. This observation sets the lung aside from other tissues in which ACKR2 is exclusively expressed on lymphatic endothelial cells and suggest unique roles for ACKR2 in the pulmonary environment.

Keywords: ACKR2; Alexa-Fluor labeling; Blood endothelial cells; Lung; Pulmonary immunity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carbocyanines / chemistry
  • Endothelial Cells / cytology
  • Endothelial Cells / immunology*
  • Epithelial Cell Adhesion Molecule / genetics
  • Epithelial Cell Adhesion Molecule / immunology
  • Flow Cytometry
  • Fluorescent Dyes / chemistry
  • Gene Expression
  • Lung / blood supply
  • Lung / cytology
  • Lung / immunology*
  • Mice
  • Mice, Knockout
  • Receptors, Chemokine / genetics
  • Receptors, Chemokine / immunology*
  • Staining and Labeling / methods
  • Stromal Cells / cytology
  • Stromal Cells / immunology*

Substances

  • Ackr2 protein, mouse
  • Alexa Fluor 647
  • Carbocyanines
  • Epithelial Cell Adhesion Molecule
  • Fluorescent Dyes
  • Receptors, Chemokine