Novel Reprogramming of Neutrophils Modulates Inflammation Resolution During Atherosclerosis

Overview

Journal Sci Adv

Specialties Biology
Science

Date 2019 Feb 19

PMID 30775441

Citations 41

Authors

Shuo Geng

Yao Zhang

Christina Lee

Liwu Li

Affiliations

Soon will be listed here.

Abstract

Nonresolving inflammation perpetuated by innate leukocytes is involved in the pathogenesis of unstable atherosclerosis. However, the role and regulation of neutrophils related to nonresolving inflammation and atherosclerosis are poorly understood. We report herein that chronic subclinical endotoxemia, a risk factor for atherosclerosis, skewed neutrophils into a nonresolving inflammatory state with elevated levels of inflammatory mediators (Dectin-1, MMP9, and LTB4) and reduced levels of homeostatic mediators (LRRC32, TGFβ, and FPN). The polarization of neutrophils was due to ROS-mediated activation of oxCAMKII, caused by altered peroxisome homeostasis and reduced lysosome fusion. Application of 4-phenylbutyrate (4-PBA) enhanced peroxisome homeostasis of neutrophils, reduced oxCAMKII, and rebalanced the expression profiles of pro- and anti-inflammatory mediators. Adoptive transfer of neutrophils programmed by subclinical endotoxemia rendered exacerbated atherosclerosis. In contrast, transfer of ex vivo programmed neutrophils by 4-PBA reduced the pathogenesis of atherosclerosis. Our data define novel neutrophil dynamics associated with the progression and regression of atherosclerosis.

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