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Journal of Clinical Immunology
Published in: Journal of Clinical Immunology 3/2013

01-04-2013 | Original Research

N-acetylcysteine Administration is Associated with Reduced Activation of NF-kB and Preserves Lung Dendritic Cells Function in a Zymosan-Induced Generalized Inflammation Model

Authors: Hong-Wei Wang, Wen Yang, Jiang-Yang Lu, Fei Li, Jun-Zhong Sun, Wen Zhang, Nan-Nan Guo, Lei Gao, Jia-Rui Kang

Published in: Journal of Clinical Immunology | Issue 3/2013

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Abstract

Purpose

In severe sepsis, functional impairment and decreased numbers of dendritic cells (DCs) are essential reasons for immune function paralysis, secondary organ infection, and organ failure. We investigated the effects of N-acetylcysteine (NAC) administration on protecting lung DCs function in a zymosan-induced generalized inflammation (ZIGI) model.

Methods

ZIGI was initiated in 80 Balb/c mice by intraperitoneal injection of zymosan (ZYM; 900 mg/kg). Mice were divided into 4 groups: (1) SHAM+Vehicle; (2) SHAM+NAC; (3) ZYM+Vehicle; and (4) ZYM+NAC. NAC (100 mg/kg) was administered at different time after ZYM injection. After 48 h, we assessed: lung tissue pathological changes; arterial blood gas values; purified lung DCs surface expressions of MHC-II/I-Ad and co-stimulatory molecules CD80, CD83, and CD86; lung DCs mRNA levels of chemokine receptors CCR5 and CCR7; lung DCs apoptosis; lung DCs ultrastructure by transmission electron microscopy; lung DCs NF-kB transcription factor activity; and LPS-stimulated lung DCs in vitro production of IL-12 and IL-10 were examined.

Results

NAC treatment resulted in: significant improvements in ZYM-induced lung tissue damage and impaired lung function; inhibited lung DCs ZYM-induced increased expression of MHC-II/I-Ad, CD83, and CD86, but not CD80; reduced lung DCs ZYM-induced CCR5 and CCR7 mRNA levels; suppressed ZYM-induced lung DCs apoptosis; ameliorated ZYM-induced lung DCs ultrastructural abnormalities; inhibited ZYM-induced lung DCs NF-κB activity; and enhanced lung DCs production of IL-12 and inhibited their production of IL-10.

Conclusions

Repeated injections of NAC during the early stage of severe sepsis effectively inhibited lung DCs activation and their apoptosis, which could preserve DCs function.
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Metadata
Title
N-acetylcysteine Administration is Associated with Reduced Activation of NF-kB and Preserves Lung Dendritic Cells Function in a Zymosan-Induced Generalized Inflammation Model
Authors
Hong-Wei Wang
Wen Yang
Jiang-Yang Lu
Fei Li
Jun-Zhong Sun
Wen Zhang
Nan-Nan Guo
Lei Gao
Jia-Rui Kang
Publication date
01-04-2013
Publisher
Springer US
Published in
Journal of Clinical Immunology / Issue 3/2013
Print ISSN: 0271-9142
Electronic ISSN: 1573-2592
DOI
https://doi.org/10.1007/s10875-012-9852-3

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