LPS exposure alleviates multiple tissues damage by facilitating macrophage efferocytosis

Yuwen Han; Jiukun Hu; Jinlin Pan; Xueyan Song; Yuanshuai Zhou; Jun Zhang; Yue Yang; Xiaohua Shi; Jiao Yang; Minxuan Sun

doi:10.1016/j.intimp.2024.112283

LPS exposure alleviates multiple tissues damage by facilitating macrophage efferocytosis

Int Immunopharmacol. 2024 Jun 30:135:112283. doi: 10.1016/j.intimp.2024.112283. Epub 2024 May 20.

Authors

Yuwen Han¹, Jiukun Hu¹, Jinlin Pan¹, Xueyan Song², Yuanshuai Zhou¹, Jun Zhang¹, Yue Yang³, Xiaohua Shi⁴, Jiao Yang⁵, Minxuan Sun⁶

Affiliations

¹ School of Biomedical Engineering (Suzhou), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, China; Jiangsu Key Lab of Medical Optics, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Keling Road No. 88, Suzhou 215163, China.
² Jiangsu Key Lab of Medical Optics, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Keling Road No. 88, Suzhou 215163, China.
³ Jiangsu Key Lab of Medical Optics, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Keling Road No. 88, Suzhou 215163, China; Department of Chemistry, College of Sciences, Shanghai University, Shanghai 200444, China.
⁴ Department of Gastroenterology, Suzhou Hospital, Affiliated Hospital of Medical School, Nanjing University, No. 1 Lijiang Road, Suzhou 215153, China.
⁵ Institute of Clinical Medicine Research, Suzhou Hospital, Affiliated Hospital of Medical School, Nanjing University, Lijiang Road No. 1, Suzhou 215153, China. Electronic address: yangjiaomed@126.com.
⁶ School of Biomedical Engineering (Suzhou), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, China; Jiangsu Key Lab of Medical Optics, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Keling Road No. 88, Suzhou 215163, China. Electronic address: minxuan.sun@sibet.ac.cn.

PMID: 38772299
DOI: 10.1016/j.intimp.2024.112283

Abstract

Toll-like receptors (TLRs) play a crucial role in mediating immune responses by recognizing pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPs), as well as facilitating apoptotic cell (ACs) clearance (efferocytosis), thus contributing significantly to maintaining homeostasis and promoting tissue resolution. In this study, we investigate the impact of TLR agonists on macrophage efferocytosis. Our findings demonstrate that pretreatment with the TLR agonist lipopolysaccharide (LPS) significantly enhances macrophage phagocytic ability, thereby promoting efferocytosis both in vitro and in vivo. Moreover, LPS pretreatment confers tissue protection against damage by augmenting macrophage efferocytic capacity in murine models. Further examination reveals that LPS modulates efferocytosis by upregulating the expression of Tim4.These results underscore the pivotal role of TLR agonists in regulating the efferocytosis process and suggest potential therapeutic avenues for addressing inflammatory diseases. Overall, our study highlights the intricate interplay between LPS pretreatment and efferocytosis in maintaining tissue homeostasis and resolving inflammation.

Keywords: Efferocytosis; Inflammation; LPS; Macrophage; Tissue resolution.

MeSH terms

Animals
Apoptosis / drug effects
Efferocytosis
Humans
Inflammation / drug therapy
Inflammation / immunology
Lipopolysaccharides*
Macrophages* / drug effects
Macrophages* / immunology
Macrophages* / metabolism
Male
Membrane Proteins / metabolism
Mice
Mice, Inbred C57BL*
Phagocytosis* / drug effects
RAW 264.7 Cells
Toll-Like Receptors / agonists
Toll-Like Receptors / metabolism

Substances

Lipopolysaccharides
TIM-4 protein, mouse
Toll-Like Receptors
Membrane Proteins