NDLI: Definition of a Novel Pathway Centered on Lysophosphatidic Acid To Recruit Monocytes during the Resolution Phase of Tissue Inflammation.

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Definition of a Novel Pathway Centered on Lysophosphatidic Acid To Recruit Monocytes during the Resolution Phase of Tissue Inflammation.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Reutelingsperger, Christopher P. Flower, Roderick J. Kusters, Dennis H. M. McArthur, Simon Gobbetti, Thomas Perretti, Mauro
Description	Author Affiliation: McArthur S ( William Harvey Research Institute, Barts and London School of Medicine, Queen Mary University of London, London, EC1M 6BQ, United Kingdom); Gobbetti T ( William Harvey Research Institute, Barts and London School of Medicine, Queen Mary University of London, London, EC1M 6BQ, United Kingdom); Kusters DH ( CARIM School for Cardiovascular Diseases, Maastricht University, 6200 MD Maastricht, the Netherlands); Reutelingsperger CP ( CARIM School for Cardiovascular Diseases, Maastricht University, 6200 MD Maastricht, the Netherlands); Flower RJ ( William Harvey Research Institute, Barts and London School of Medicine, Queen Mary University of London, London, EC1M 6BQ, United Kingdom); Perretti M ( William Harvey Research Institute, Barts and London School of Medicine, Queen Mary University of London, London, EC1M 6BQ, United Kingdom)
Abstract	Blood-derived monocytes remove apoptotic cells and terminate inflammation in settings as diverse as atherosclerosis and Alzheimer's disease. They express high levels of the proresolving receptor ALX/FPR2, which is activated by the protein annexin A1 (ANXA1), found in high abundance in inflammatory exudates. Using primary human blood monocytes from healthy donors, we identified ANXA1 as a potent CD14(+)CD16(-) monocyte chemoattractant, acting via ALX/FPR2. Downstream signaling pathway analysis revealed the p38 MAPK-mediated activation of a calcium independent phospholipase A2 with resultant synthesis of lysophosphatidic acid (LPA) driving chemotaxis through LPA receptor 2 and actin cytoskeletal mobilization. In vivo experiments confirmed ANXA1 as an independent phospholipase A2-dependent monocyte recruiter; congruently, monocyte recruitment was significantly impaired during ongoing zymosan-induced inflammation in AnxA1(-/-) or alx/fpr2/3(-/-) mice. Using a dorsal air-pouch model, passive transfer of apoptotic neutrophils between AnxA1(-/-) and wild-type mice identified effete neutrophils as the primary source of soluble ANXA1 in inflammatory resolution. Together, these data elucidate a novel proresolving network centered on ANXA1 and LPA generation and identify previously unappreciated determinants of ANXA1 and ALX/FPR2 signaling in monocytes.
ISSN	00221767
e-ISSN	15506606
DOI	10.4049/jimmunol.1500733
Journal	The Journal of Immunology
Issue Number	3
Volume Number	195
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2015-08-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Annexin A1 Immunology Apoptosis Monocytes Neutrophils Receptors, Lysophosphatidic Acid Actin Cytoskeleton Metabolism Animals Genetics Antigens, Cd14 Cells, Cultured Enzyme Activation Inflammation Lysophospholipids Biosynthesis Mice Mice, Inbred C57bl Mice, Knockout Transplantation Phospholipases A2, Calcium-independent Rna Interference Rna, Small Interfering Receptors, Formyl Peptide Receptors, Igg Zymosan P38 Mitogen-activated Protein Kinases Research Support, Non-u.s. Gov't Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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