Dysfunctional phagocytosis capacity, granulocyte recruitment and inflammatory factor secretion of Kupffer cells in diabetes mellitus reversed by Lidocaine

Abstract

Purpose

Kupffer cells (KCs) present dysfunctional immunity capacity among the diabetes mellitus patients. This study aims to investigate whether Lidocaine could reverse dysfunctions of KCs, in terms of phagocytosis, granulocyte recruitment and inflammatory mediator secretion.

Methods

db/db and C57BL/6 mice were employed to establish diabetic and nondiabetic models. Upon intravenous injection of Lidocaine, KCs were isolated and cultured ex vivo. The functions of phagocytosis, recruiting granulocytes and inflammatory mediator secretion in KCs were compared between Lidocaine-treated and untreated (control) groups.

Results

Comparing with nondiabetic mice, KCs in diabetic mice presented reduced phagocytosis, activated granulocyte recruitment, increased expression of intercellular cell adhesion molecule-1 (ICAM-1) and activated levels of inflammatory mediators. With Lidocaine injection, phagocytic functions of KCs in diabetic mice were improved significantly; in contrast, recruitment of granulocytes, expression of ICAM-1 and secretion of inflammatory mediators were reduced markedly. However, Lidocaine intervention did not alter KC functions in phagocytosis, granulocyte recruitment, ICAM-1 expression or inflammatory mediator secretion among nondiabetic mice.

Conclusion

Lidocaine reversed diabetes-related dysfunctions of KCs in terms of phagocytosis, granulocyte recruitment, ICAM-1 expression or inflammatory mediator secretion.

Keywords:

• macrophages
• diabetes
• phagocytosis
• granulocyte recruitment
• inflammatory mediator
• Lidocaine

Acknowledgments

This study was supported by Beijing Shijitan Hospital (RW. 2016-Q18), Ministry of Railway (QS. grant number J2017Z604) and Beijing Municipal Administration of Hospitals (QS. grant number PX2018029). The supporting organizations had no role in study design, data collection, analysis and interpretation.

Author contributions

Study design: QS, MS and RW. Data acquisition: FS, YZ, LZ and GW. Data analysis: QS, LZ and JW. Manuscript writing and modification: QS, FS, RW, YZ, LZ, JW, MS and GW. Submission approval: QS, FS, RW, YZ, LZ, JW, MS and GW. All authors contributed to data analysis, drafting and revising the article, gave final approval of the version to be published, and agree to be accountable for all aspects of the work.

Disclosure

The author reports no conflicts of interest in this work.