Abstract:
: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-gamma, 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.
journal_name
Am J Respir Cell Mol Biolauthors
Roghanian A,Williams SE,Sheldrake TA,Brown TI,Oberheim K,Xing Z,Howie SE,Sallenave JMdoi
10.1165/rcmb.2005-0405OCkeywords:
subject
Has Abstractpub_date
2006-05-01 00:00:00pages
634-42issue
5eissn
1044-1549issn
1535-4989pii
2005-0405OCjournal_volume
34pub_type
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