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

摘要: Blood-derived monocytes remove apoptotic cells and terminate inflammation in settings as diverse atherosclerosis Alzheimer’s disease. They express high levels of the proresolving receptor ALX/FPR2, which is activated by protein annexin A1 (ANXA1), found abundance inflammatory exudates. Using primary human blood from healthy donors, we identified ANXA1 a potent CD14+CD16− monocyte chemoattractant, acting via ALX/FPR2. Downstream signaling pathway analysis revealed p38 MAPK-mediated activation calcium independent phospholipase A2 with resultant synthesis lysophosphatidic acid (LPA) driving chemotaxis through LPA 2 actin cytoskeletal mobilization. In vivo experiments confirmed an A2–dependent recruiter; congruently, recruitment was significantly impaired during ongoing zymosan-induced AnxA1−/− or alx/fpr2/3−/− mice. dorsal air-pouch model, passive transfer neutrophils between wild-type mice effete source soluble resolution. Together, these data elucidate novel network centered on generation identify previously unappreciated determinants ALX/FPR2 monocytes.