Spleen-derived classical monocytes mediate lung ischemia-reperfusion injury through IL-1ß

Hsi Min Hsiao, Ramiro Fernandez, Satona Tanaka, Wenjun Li, Jessica H. Spahn, Stephen Chiu, Mahzad Akbarpour, Daniel Ruiz-Perez, Qiang Wu, Cem Turam, Davide Scozzi, Tsuyoshi Takahashi, Hannah P. Luehmann, Varun Puri, G. R.Scott Budinger, Alexander S. Krupnick, Alexander V. Misharin, Kory J. Lavine, Yongjian Liu, Andrew E. GelmanAnkit Bharat*, Daniel Kreisel

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

Ischemia-reperfusion injury, a form of sterile inflammation, is the leading risk factor for both short-term mortality following pulmonary transplantation and chronic lung allograft dysfunction. While it is well recognized that neutrophils are critical mediators of acute lung injury, processes that guide their entry into pulmonary tissue are not well understood. Here, we found that CCR2+ classical monocytes are necessary and sufficient for mediating extravasation of neutrophils into pulmonary tissue during ischemia-reperfusion injury following hilar clamping or lung transplantation. The classical monocytes were mobilized from the host spleen, and splenectomy attenuated the recruitment of classical monocytes as well as the entry of neutrophils into injured lung tissue, which was associated with improved graft function. Neutrophil extravasation was mediated by MyD88-dependent IL-1ß production by graft-infiltrating classical monocytes, which downregulated the expression of the tight junction–associated protein ZO-2 in pulmonary vascular endothelial cells. Thus, we have uncovered a crucial role for classical monocytes, mobilized from the spleen, in mediating neutrophil extravasation, with potential implications for targeting of recipient classical monocytes to ameliorate pulmonary ischemia-reperfusion injury in the clinic.

Original languageEnglish (US)
Pages (from-to)2833-2847
Number of pages15
JournalJournal of Clinical Investigation
Volume128
Issue number7
DOIs
StatePublished - Jul 2 2018

ASJC Scopus subject areas

  • Medicine(all)

Fingerprint

Dive into the research topics of 'Spleen-derived classical monocytes mediate lung ischemia-reperfusion injury through IL-1ß'. Together they form a unique fingerprint.

Cite this