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

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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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Acknowledgments

This study was supported by grants from the National Natural Science Foundation (Project No. 81000848) of China and the Capital Health Research and Development of Special of China (Project No. 2011-5002-01 and No. 2011-5002-02).

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Authors and Affiliations

  1. Department of Pathology, the First Affiliated Hospital of General Hospital of Chinese People’s Liberation Army, Beijing, 100048, China

    Hong-Wei Wang, Jiang-Yang Lu, Fei Li, Jun-Zhong Sun & Jia-Rui Kang

  2. Department of Gynaecology and Obstetrics, General Hospital of Chinese People’s Liberation Army, Beijing, 100853, China

    Wen Yang

  3. Department of Thoracic Surgery, the First Affiliated Hospital of General Hospital of Chinese People’s Liberation Army, Beijing, 100048, China

    Wen Zhang & Nan-Nan Guo

  4. Department of Pharmacy, the First Affiliated Hospital of General Hospital of Chinese People’s Liberation Army, Beijing, 100048, China

    Lei Gao

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  1. Hong-Wei Wang
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Correspondence to Jiang-Yang Lu.

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Hong-Wei Wang and Wen Yang contributed equally to this work.

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Wang, HW., Yang, W., Lu, JY. et al. N-acetylcysteine Administration is Associated with Reduced Activation of NF-kB and Preserves Lung Dendritic Cells Function in a Zymosan-Induced Generalized Inflammation Model. J Clin Immunol 33, 649–660 (2013). https://doi.org/10.1007/s10875-012-9852-3

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  • DOI: https://doi.org/10.1007/s10875-012-9852-3

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