期刊
BLOOD
卷 118, 期 3, 页码 712-722出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2010-12-324186
关键词
-
类别
资金
- Wellcome Trust [WT082909MA, GR077544AIA]
- MRC [G0701932, G0700091]
- A*STAR (Singapore)
- Wellcome Intermediate Fellowship [WT078244AIA]
- MRC [G108/595, G0701932] Funding Source: UKRI
- Medical Research Council [G0700091, G108/595, G0700091B, G0701932] Funding Source: researchfish
The oxygen-sensing transcription factor hypoxia-inducible factor-1 alpha (HIF-1 alpha) plays a critical role in the regulation of myeloid cell function. The mechanisms of regulation are not well understood, nor are the phenotypic consequences of HIF modulation in the context of neutrophilic inflammation. Species conservation across higher metazoans enables the use of the genetically tractable and transparent zebrafish (Danio rerio) embryo to study in vivo resolution of the inflammatory response. Using both a pharmacologic approach known to lead to stabilization of HIF-1 alpha, and selective genetic manipulation of zebrafish HIF-1 alpha homologs, we sought to determine the roles of HIF-1 alpha in inflammation resolution. Both approaches reveal that activated Hif-1 alpha delays resolution of inflammation after tail transection in zebrafish larvae. This delay can be replicated by neutrophil-specific Hif activation and is a consequence of both reduced neutrophil apoptosis and increased retention of neutrophils at the site of tissue injury. Hif-activated neutro-phils continue to patrol the injury site during the resolution phase, when neutrophils would normally migrate away. Site-directed mutagenesis of Hif in vivo reveals that hydroxylation of Hif-1 alpha by prolyl hydroxylases critically regulates the Hif pathway in zebrafish neutrophils. Our data demonstrate that Hif-1 alpha regulates neutrophil function in complex ways during inflammation resolution in vivo. (Blood. 2011;118(3):712-722)
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据