Published ahead of print on January 19, 2006, doi:10.1165/rcmb.2005-0405OC
© 2006 American Thoracic Society DOI: 10.1165/rcmb.2005-0405OC The Antimicrobial/Elastase Inhibitor Elafin Regulates Lung Dendritic Cells and Adaptive ImmunityMRC Centre for Inflammation Research, The Queen's Medical Research Institute, Edinburgh University, Edinburgh; Wellcome Trust Centre for Research in Comparative Respiratory Medicine, Easter Bush Veterinary Centre, Roslin, United Kingdom; and Department of Pathology and Molecular Medicine and Division of Infectious Diseases, Centre for Gene Therapeutics, McMaster University, Hamilton, Ontario, Canada Correspondence and requests for reprints should be addressed to Jean-Michel Sallenave, Room W2.05, MRC Centre for Inflammation Research, Queen's Medical Research Institute, Edinburgh University, 47 Little France Crescent, Edinburgh, EH16 4TJ, Scotland, UK. E-mail: J.Sallenave{at}ed.ac.uk
Infections with bacteria and viruses such as adenovirus are a feature of chronic lung diseases such as chronic obstructive pulmonary diseases (COPD), and may be instrumental in the generation of disease exacerbations. We have previously shown in acute models that elafin (a lung natural chemotactic molecule for macrophages and neutrophils, with potent antimicrobial and neutrophil elastase inhibitor activity) is upregulated in infection and modulates innate immunity. Here we present data using two independent systems of elafin overexpression in vivo (recombinant adenovirus [Ad-elafin] and an elafin transgenic mouse line) to examine the function of elafin in adaptive immunity. We show that elafin increases the number (immunofluorescence) and activation status (flow cytometric measurement) of CD11c+/MHCII+ lung dendritic cells in vivo. Analysis of cytokines produced by spleen and lung cells, and of antibodies measured in serum and bronchoalveolar lavage fluid, shows that the immunity induced is biased toward a type 1 response (production of IL-12, IFN-
Key Words: adenovirus • chronic obstructive pulmonary diseases • dendritic cells • elafin • mucosal immunity This article has been cited by other articles:
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, and IgG2a). Furthermore, elafin overexpression protected mice against further challenge with Ad-LacZ, as assessed by antibody levels and neutralization titer, as well as LacZ expression in lung tissue. Thus, the pleiotropic molecule elafin has significant potential in modulating antigen-presenting cell numbers and activity, and could be beneficial in mucosal protective strategies. 
