Published online before print January 17, 2008

This Article Full Text Full Text (PDF) All Versions of this Article: ajpath.2008.070870v1 172/2/395    most recent Purchase Article View Shopping Cart Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Farnworth, S. L. Articles by Sethi, T. Search for Related Content PubMed PubMed Citation Articles by Farnworth, S. L. Articles by Sethi, T.

(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, 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,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.

This article has been cited by other articles:

				A. Drewniak, B. J. van Raam, J. Geissler, A. T.J. Tool, O. R.F. Mook, T. K. van den Berg, F. Baas, and T. W. Kuijpers Changes in gene expression of granulocytes during in vivo granulocyte colony-stimulating factor/dexamethasone mobilization for transfusion purposes Blood, June 4, 2009; 113(23): 5979 - 5998. [Abstract] [Full Text] [PDF]

				L. V Norling, M. Perretti, and D. Cooper Endogenous galectins and the control of the host inflammatory response J. Endocrinol., May 1, 2009; 201(2): 169 - 184. [Abstract] [Full Text] [PDF]

				A. Karlsson, K. Christenson, M. Matlak, A. Bjorstad, K. L Brown, E. Telemo, E. Salomonsson, H. Leffler, and J. Bylund Galectin-3 functions as an opsonin and enhances the macrophage clearance of apoptotic neutrophils Glycobiology, January 1, 2009; 19(1): 16 - 20. [Abstract] [Full Text] [PDF]

				H. Forsman, E. Salomonsson, K. Onnheim, J. Karlsson, A. Bjorstad, H. Leffler, J. Bylund, A. Karlsson, and C. Dahlgren The {beta}-galactoside binding immunomodulatory lectin galectin-3 reverses the desensitized state induced in neutrophils by the chemotactic peptide f-Met-Leu-Phe: role of reactive oxygen species generated by the NADPH-oxidase and inactivation of the agonist Glycobiology, November 1, 2008; 18(11): 905 - 912. [Abstract] [Full Text] [PDF]