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Originally published online as doi:10.2353/ajpath.2008.070870 on January 17, 2008

Published online before print January 17, 2008
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(American Journal of Pathology. 2008;172:395-405.)
© 2008 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2008.070870

Galectin-3 Reduces the Severity of Pneumococcal Pneumonia by Augmenting Neutrophil Function

Sarah L. Farnworth*, Neil C. Henderson*, Alison C. MacKinnon*, Kirsten M. Atkinson*, Tom Wilkinson*, Kevin Dhaliwal*, Katsutoshi Hayashi{dagger}, A. John Simpson*, Adriano G. Rossi*, Christopher Haslett* and Tariq Sethi*

From the Centre for Inflammation Research,*The Queen’s Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom; and the Department of Respiratory Medicine,{dagger}Sendai City Medical Centre, Sendai City, Japan

The Gram-positive Streptococcus pneumoniae is the leading cause of community-acquired pneumonia worldwide, resulting in high mortality. Our in vivo studies show that galectin-3–/– mice develop more severe pneumonia after infection with S. pneumoniae, as demonstrated by increased bacteremia and lung damage compared to wild-type mice and that galectin-3 reduces the severity of pneumococcal pneumonia in part by augmenting neutrophil function. Specifically, we show that 1) galectin-3 directly acts as a neutrophil-activating agent and potentiates the effect of fMLP, 2) exogenous galectin-3 augments neutrophil phagocytosis of bacteria and delays neutrophil apoptosis, 3) phagocytosis of apoptotic neutrophils by galectin-3–/– macrophages is less efficient compared to wild type, and 4) galectin-3 demonstrates bacteriostatic properties against S. pneumoniae in vitro. Furthermore, ad-back of recombinant galectin-3 in vivo protects galectin-3-deficient mice from developing severe pneumonia. Together, these results demonstrate that galectin-3 is a key molecule in the host defense against pneumococcal infection. Therapeutic strategies designed to augment galectin-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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Copyright © 2008 by the American Society for Investigative Pathology.