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<p>Pulmonary infections are characterized by neutrophil recruitment into the lung driven by chemokine ligands of CXCR2, which is expressed on neutrophils, but also present in non-hematopoietic lung cells, in which its role remains unclear. We hypothesize that CXCR2 in epithelial and endothelial cells contributes to neutrophil recruitment into the lung by modifying the availability of its cognate chemokines in lung alveoli. Using conditional endothelial and epithelial CXCR2 knockout mice, we demonstrate that selective CXCR2 deletion in either compartment impairs neutrophil recruitment into the lung during bacterial pneumonia and reduces bacterial clearance. We show that CXCR2 ablation in epithelial and endothelial cells compromises respective trans-epithelial and trans-endothelial transcytosis of alveolar CXCL1. Mechanistically, CXCR2-mediated CXCL1 endothelial and epithelial cell transcytosis requires the function of Bruton’s tyrosine kinase in these cells. In conclusion, CXCR2 plays an important role in alveolar epithelial and endothelial cells, where it mediates cognate chemokine transcytosis, thus actively supporting their activities in neutrophil recruitment to the infected lungs.</p>

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Alveolar epithelial and vascular CXCR2 mediates transcytosis of CXCL1 in inflamed lungs

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年5月24日

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  • Katharina Thomas,
  • Jan Rossaint,
  • Nadine Ludwig,
  • Sina Mersmann,
  • Niklas Kötting,
  • Julia Grenzheuser,
  • Lena Schemmelmann,
  • Marina Oguama,
  • Andreas Margraf,
  • Helena Block,
  • Katharina Henke,
  • Katharina Hellenthal,
  • Valbona Mirakaj,
  • Volker Gerke,
  • Uwe Hansen,
  • Karin Gäher,
  • Miguel Engelhardt,
  • Johannes Roth,
  • Johannes Eble,
  • Elin Hub,
  • Antal Rot,
  • Ronen Alon,
  • Alexander Zarbock

摘要

Pulmonary infections are characterized by neutrophil recruitment into the lung driven by chemokine ligands of CXCR2, which is expressed on neutrophils, but also present in non-hematopoietic lung cells, in which its role remains unclear. We hypothesize that CXCR2 in epithelial and endothelial cells contributes to neutrophil recruitment into the lung by modifying the availability of its cognate chemokines in lung alveoli. Using conditional endothelial and epithelial CXCR2 knockout mice, we demonstrate that selective CXCR2 deletion in either compartment impairs neutrophil recruitment into the lung during bacterial pneumonia and reduces bacterial clearance. We show that CXCR2 ablation in epithelial and endothelial cells compromises respective trans-epithelial and trans-endothelial transcytosis of alveolar CXCL1. Mechanistically, CXCR2-mediated CXCL1 endothelial and epithelial cell transcytosis requires the function of Bruton’s tyrosine kinase in these cells. In conclusion, CXCR2 plays an important role in alveolar epithelial and endothelial cells, where it mediates cognate chemokine transcytosis, thus actively supporting their activities in neutrophil recruitment to the infected lungs.