Neutrophil-Derived Cathelicidin Promotes Adhesion of Classical Monocytes

Sarawuth Wantha, Jean-Eric Alard, Remco T. A. Megens, Anne M. van der Does, Yvonne Doering, Maik Drechsler, Christine T. N. Pham, Ming-Wei Wang, Ji-Min Wang, Richard L. Gallo, Philipp von Hundelshausen, Lennart Lindbom, Tilman Hackeng, Christian Weber, Oliver Soehnlein*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

110 Citations (Web of Science)

Abstract

Rationale: The leukocyte response in acute inflammation is characterized by an initial recruitment of neutrophils preceding a second wave of monocytes. Neutrophil-derived granule proteins were suggested to hold an important role in this cellular switch. The exact mechanisms by which neutrophils mediate these processes are only partially understood. Objective: To investigate the role of neutrophils and their granule contents in the adhesion of monocyte subpopulations in acute inflammation. Methods and Results: Here, we show that neutrophil-derived cathelicidins (human: LL37, mouse: CRAMP) induce adhesion of classical monocytes but not of nonclassical monocytes in the mouse cremaster muscle and in in vitro flow chamber assays. CRAMP is released from emigrated neutrophils and then transported across the endothelium, where it is presented to rolling leukocytes. Endothelial-bound cathelicidin activates formyl-peptide receptor 2 on classical monocytes, resulting in monocytic beta(1)- and beta(2)-integrin conformational change toward an extended, active conformation that allows for adhesion to their respective ligands, vascular cell adhesion molecule 1 and intercellular adhesion molecule 1. Conclusions: These data elucidate a novel mechanism of neutrophil-mediated monocyte recruitment, which could be targeted in conditions where recruitment of classical monocytes plays an unfavorable role. (Circ Res. 2013;112:792-801.)
Original languageEnglish
Pages (from-to)792-801
JournalCirculation Research
Volume112
Issue number5
DOIs
Publication statusPublished - 1 Mar 2013

Keywords

  • cathelicidin
  • chemokine
  • inflammation
  • monocyte
  • neutrophil
  • recruitment

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