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Open Access Highly Accessed Research

Immunomodulatory strategies prevent the development of autoimmune emphysema

Masayuki Hanaoka1, Mark R Nicolls2, Andrew P Fontenot1, Donatas Kraskauskas3, Douglas G Mack1, Adelheid Kratzer1, Jonas Salys1, Vita Kraskauskiene3, Nana Burns1, Norbert F Voelkel3 and Laimute Taraseviciene-Stewart1*

Author Affiliations

1 Department of Medicine, University of Colorado Denver, Aurora, CO, 80045, USA

2 VA Palo Alto Health Care System, Stanford University, Palo Alto, CA, 94304, USA

3 Pulmonary and Critical Care Medicine Division and Virginia Johnson Center for Emphysema Research, Virginia Commonwealth University, Richmond, VA, 23298, USA

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Respiratory Research 2010, 11:179  doi:10.1186/1465-9921-11-179

Published: 16 December 2010

Abstract

Background

The presence of anti-endothelial cell antibodies and pathogenic T cells may reflect an autoimmune component in the pathogenesis of emphysema. Whether immune modulatory strategies can protect against the development of emphysema is not known.

Methods

Sprague Dawley rats were immunized with human umbilical vein endothelial cells (HUVEC) to induce autoimmune emphysema and treated with intrathymic HUVEC-injection and pristane. Measurements of alveolar airspace enlargement, cytokine levels, immuno histochemical, western blot analysis, and T cell repertoire of the lung tissue were performed.

Results

The immunomodulatory strategies protected lungs against cell death as demonstrated by reduced numbers of TUNEL and active caspase-3 positive cells and reduced levels of active caspase-3, when compared with lungs from HUVEC-immunized rats. Immunomodulatory strategies also suppressed anti-endothelial antibody production and preserved CNTF, IL-1alpha and VEGF levels. The immune deviation effects of the intrathymic HUVEC-injection were associated with an expansion of CD4+CD25+Foxp3+ regulatory T cells. Pristane treatment decreased the proportion of T cells expressing receptor beta-chain, Vβ16.1 in the lung tissue.

Conclusions

Our data demonstrate that interventions classically employed to induce central T cell tolerance (thymic inoculation of antigen) or to activate innate immune responses (pristane treatment) can prevent the development of autoimmune emphysema.