Published ahead of print on January 19, 2006, doi:10.1165/rcmb.2005-0405OC Am. J. Respir. Cell Mol. Biol., Volume 34, Number 5, May 2006, 634-642 A more recent version of this article appeared on May 1, 2006
Submitted on October 31, 2005 The Antimicrobial/Elastase Inhibitor Elafin Regulates Lung Dendritic Cells and Adaptive ImmunityAli Roghanian1,1 MRC Centre for Inflammation Research, The Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom, 2 MRC Centre for Inflammation Research, The Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom; Wellcome Trust Centre for Research in Comparative Respiratory Medicine, Easter Bush Veternary Centre, Roslin, Edinburgh, United Kingdom, 3 Department of Pathology and Molecular Medicine and the Division of Infectious Diseases, Centre for Gene Therapeutics, McMaster University, Hamilton, Canada, 4 Centre for Inflammation Research, Immunobiology Group, The Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom * To whom correspondence should be addressed. 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 over-expression in vivo [recombinant adenovirus (Adelafin) 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, antibodies measured in serum and bronchoalveolar lavage fluid, shows that the immunity induced is biased towards a type 1 response (production of IL-12, IFN-
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and IgG2a). Furthermore, elafin-over-expression protected mice against further challenge with Ad-LacZ, as assessed by antibody levels and neutralisation titre, 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.
