Source: International Congress 2015 – Advances from translational research in respiratory infections
Disease area: Airway diseases

Abstract

Introduction: Cigarette smoke negates the anti-inflammatory effects of protein tyrosine phosphatase 1B (PTP1B). Additionally, respiratory syncytial viral (RSV), a cause of chronic obstructive pulmonary disease (COPD) exacerbations, also reduces airway PTP1B activity. Reduced PTP1B correlates with COPD severity in smoked RSV infected mice. However the exact role of PTP1B in virus-associated COPD exacerbations is unknown. To determine the impact of PTP1B in RSV infection, Ptp1b knockout (-/-) animals were investigated in RSV-induced COPD exacerbations models.Methods: Ptp1b^-/- mice (FVB.129S4(B6)-Ptpn1^tm1Bbk/Mmjax) and wild-type littermates were exposed to 4 months of cigarette smoke or room air and subsequently infected with RSV or a mock control. RSV exposures were also performed in epithelial cells from healthy and COPD donors. Airway cytokine production, apoptosis and remodeling were investigated.Results: Loss of PTP1B expression enhanced smoke-induced airway enlargements. RSV infection caused greater airway damage in Ptp1b^-/- mice, with exaggerated inflammation, damaged epithelium and increased apoptosis compared to wild-type littermates. There was increased gene expression of S100A9, a damage-associated molecular patterns molecule, in the airways of Ptp1b^-/- mice during RSV infection. Treatment with neutralizing anti-S100A9 IgG reduced RSV-pathology with reduced airspace protein, immune cell recruitment, cytokine production and apoptosis.Conclusions: Loss of PTP1B activity in the airways may contribute to the enhanced disease progression during viral-associated COPD exacerbations. Indeed, PTP1B regulation of S100A9 may play a key role in lung injury.


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Robert Foronjy (Scarsdale, United States of America), Pius Ochieng, Edward Eden, Matthias Salathe, Abdoulaye Dabo, Nathalie Schmid, Michael Campos, Neville Cummins, Robert Foronjy, Patrick Geraghty. Protein tyrosine phosphatase 1B negatively regulates S100A9 mediated apoptosis during respiratory syncytial virus infection. Eur Respir J 2015; 46: Suppl. 59, 5038

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