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Role of inducible nitric oxide synthase expressed by alveolar macrophages in High Mobility Group Box 1- induced acute lung injury

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Abstract.

Objective and design

The role of inducible nitric oxide synthase (iNOS) expressed by alveolar macrophages in acute lung injury induced by high mobility group box 1 (HMGB1) was explored.

Treatments

Primary rat alveolar macrophages (PRAMs) were stimulated with HMGB1 to analyze iNOS expression. Alveolar macrophages and iNOS were inhibited by gadolinium chloride and 1400W in rats challenged by HMGB1 intratracheally.

Methods

Western Blot was applied to assay iNOS expression in PRAMs. Indices for acute lung injury in rats were measured. Immunocytochemistry was used to localize iNOS in□bronchoalveolar lavage (BAL) cells. The enzyme activities of iNOS and constitutive nitric oxide synthase (cNOS) for BAL cells were determined.

Results

A time- and concentration-dependent response of iNOS expression in PRAMs to HMGB1 induction was observed. Intratracheal instillation of HMGB1 produced persistently exacerbated acute lung inflammation, induction of iNOS in alveolar macrophages and increased lung nitric oxide production in rats. Abrogation of iNOS or macrophages attenuated lung inflammation, nitric oxide in BAL fluid, and iNOS activity of BAL cells, but had no significant effect on cNOS activity of BAL cells in rats challenged by HMGB1.

Conclusions

Inducible nitric oxide synthase expressed by alveolar macrophages facilitates the development of HMGB1-induced acute lung injury.

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Authors and Affiliations

  1. Department of Pathophysiology, Institute of Basic Medical Sciences, Peking Union Medical College & Chinese Academy of Medical Sciences, 5 Dong Dan San Tiao, Beijing, 100005, People’s Republic of China

    D. Ren & R. Sun

  2. The Institute of Geriatric Cardiology, Chinese People’s Liberation Army General Hospital, Beijing, 100005, People’s Republic of China

    S. Wang

Authors
  1. D. Ren
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  2. R. Sun
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  3. S. Wang
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Corresponding author

Correspondence to D. Ren.

Additional information

Received 12 March 2005; returned for revision 11 January 2006; accepted by M. Parnham 24 January 2006

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Ren, D., Sun, R. & Wang, S. Role of inducible nitric oxide synthase expressed by alveolar macrophages in High Mobility Group Box 1- induced acute lung injury. Inflamm. res. 55, 207–215 (2006). https://doi.org/10.1007/s00011-006-0072-2

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  • DOI: https://doi.org/10.1007/s00011-006-0072-2

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