Galectin-3 reduces the severity of pneumococcal pneumonia by augmenting neutrophil function
S. Farnworth, N. Henderson, A. Mackinnon, K. Atkinson, T. Wilkinson, K. Dhaliwal, J. Simpson, A. Rossi, C. Haslett, T. Sethi (Edinburgh, United Kingdom)
Source: Annual Congress 2008 - Mechanisms of respiratory infections: interaction between the pathogen and the host
Disease area: Respiratory infections
Abstract Streptococcus pneumoniae (S. pn ) is the leading cause of community-acquired pneumonia worldwide, resulting in high mortality. Galectin-3 (gal-3), a beta-galactoside binding lectin implicated in many facets of the inflammatory response, accumulates in the lungs of mice infected with S. pn correlating with onset of neutrophil extravasation. We tested the hypothesis that gal-3 reduces the severity of pneumococcal pneumonia by augmenting neutrophil function using both in vivo and in vitro techniques. In vivo , gal-3 deficient (gal-3-/-) mice develop more severe pneumonia following S. pn infection, as demonstrated by increased bacteraemia and lung damage compared to wild-type mice. In vitro we show that 1) gal-3 directly acts as a neutrophil-activating agent and potentiates the effect of fMLP, 2) exogenous gal-3 augments neutrophil phagocytosis of bacteria and delays neutrophil apoptosis, 3) phagocytosis of apoptotic neutrophils by gal-3-/- macrophages is less efficient compared to wild type, 4) gal-3 demonstrates bacteriostatic properties against S. pn . Furthermore, add-back of recombinant gal-3 in vivo protects gal-3-/- mice from developing severe pneumonia. Together, these results demonstrate that gal-3 is a key molecule in the host defense against pneumococcal infection. Therapeutic strategies designed to augment gal-3 activity may both enhance inflammatory cell function (by directly affecting neutrophil responsiveness and prolonging neutrophil longevity) and have direct bacteriostatic activity, improving clinical outcomes after severe pneumococcal infection.
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S. Farnworth, N. Henderson, A. Mackinnon, K. Atkinson, T. Wilkinson, K. Dhaliwal, J. Simpson, A. Rossi, C. Haslett, T. Sethi (Edinburgh, United Kingdom). Galectin-3 reduces the severity of pneumococcal pneumonia by augmenting neutrophil function. Eur Respir J 2008; 32: Suppl. 52, 2286
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