Neutrophil-Derived Cathelicidin Promotes Adhesion of Classical Monocytes
- 1 March 2013
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Circulation Research
- Vol. 112 (5), 792-801
- https://doi.org/10.1161/circresaha.112.300666
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 β1- and β2-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.Keywords
This publication has 56 references indexed in Scilit:
- Neutrophil-Derived Cathelicidin Protects from Neointimal HyperplasiaScience Translational Medicine, 2011
- Caveolin‐1 deficiency decreases atherosclerosis by hampering leukocyte influx into the arterial wall and generating a regulatory T‐cell responseThe FASEB Journal, 2011
- Impaired Infarct Healing in Atherosclerotic Mice With Ly-6ChiMonocytosisJournal of the American College of Cardiology, 2010
- Development of Monocytes, Macrophages, and Dendritic CellsScience, 2010
- Monocytes in atherosclerosis: subsets and functionsNature Reviews Cardiology, 2010
- Alarmins link neutrophils and dendritic cellsTrends in Immunology, 2009
- Evidence that cathelicidin peptide LL‐37 may act as a functional ligand for CXCR2 on human neutrophilsEuropean Journal of Immunology, 2009
- Regulation of the Migration and Survival of Monocyte Subsets by Chemokine Receptors and Its Relevance to AtherosclerosisArteriosclerosis, Thrombosis, and Vascular Biology, 2009
- The Duffy antigen receptor for chemokines transports chemokines and supports their promigratory activityNature Immunology, 2008
- In Silico Identification and Biological Evaluation of Antimicrobial Peptides Based on Human Cathelicidin LL-37Antimicrobial Agents and Chemotherapy, 2006