Leukotriene B4 receptor 2 governs macrophage migration during tissue inflammation.

Autor:	Ermis E; Kovler Diabetes Center, The University of Chicago, Chicago, Illinois, USA; The College, The University of Chicago, Chicago, Illinois, USA., Nargis T; Kovler Diabetes Center, The University of Chicago, Chicago, Illinois, USA; Department of Medicine, The University of Chicago, Chicago, Illinois, USA., Webster K; Kovler Diabetes Center, The University of Chicago, Chicago, Illinois, USA; Department of Medicine, The University of Chicago, Chicago, Illinois, USA., Tersey SA; Kovler Diabetes Center, The University of Chicago, Chicago, Illinois, USA; Department of Medicine, The University of Chicago, Chicago, Illinois, USA., Anderson RM; Kovler Diabetes Center, The University of Chicago, Chicago, Illinois, USA; Department of Medicine, The University of Chicago, Chicago, Illinois, USA. Electronic address: ryananderson@uchicago.edu., Mirmira RG; Kovler Diabetes Center, The University of Chicago, Chicago, Illinois, USA; The College, The University of Chicago, Chicago, Illinois, USA; Department of Medicine, The University of Chicago, Chicago, Illinois, USA; Department of Pediatrics, The University of Chicago, Chicago, Illinois, USA. Electronic address: mirmira@uchicago.edu.
Jazyk:	angličtina
Zdroj:	The Journal of biological chemistry [J Biol Chem] 2024 Jan; Vol. 300 (1), pp. 105561. Date of Electronic Publication: 2023 Dec 12.
DOI:	10.1016/j.jbc.2023.105561
Abstrakt:	Chronic inflammation is the underlying cause of many diseases, including type 1 diabetes, obesity, and non-alcoholic fatty liver disease. Macrophages are continuously recruited to tissues during chronic inflammation where they exacerbate or resolve the pro-inflammatory environment. Although leukotriene B4 receptor 2 (BLT2) has been characterized as a low affinity receptor to several key eicosanoids and chemoattractants, its precise roles in the setting of inflammation and macrophage function remain incompletely understood. Here we used zebrafish and mouse models to probe the role of BLT2 in macrophage function during inflammation. We detected BLT2 expression in bone marrow derived and peritoneal macrophages of mouse models. Transcriptomic analysis of Ltb4r2-/- and WT macrophages suggested a role for BLT2 in macrophage migration, and studies in vitro confirmed that whereas BLT2 does not mediate macrophage polarization, it is required for chemotactic function, possibly mediated by downstream genes Ccl5 and Lgals3. Using a zebrafish model of tailfin injury, we demonstrated that antisense morpholino-mediated knockdown of blt2a or chemical inhibition of BLT2 signaling impairs macrophage migration. We further replicated these findings in zebrafish models of islet injury and liver inflammation. Moreover, we established the applicability of our zebrafish findings to mammals by showing that macrophages of Ltb4r2-/- mice have defective migration during lipopolysaccharide stimulation in vivo. Collectively, our results demonstrate that BLT2 mediates macrophage migration during inflammation, which implicates it as a potential therapeutic target for inflammatory pathologies. Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article. (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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