| Title | Galectin-3 reduces the severity of pneumococcal pneumonia by augmenting neutrophil function. |
| Publication Type | Journal Article |
| Year of Publication | 2008 |
| Authors | Farnworth SL, Henderson NC, Mackinnon AC, Atkinson KM, Wilkinson T, Dhaliwal K, Hayashi K, Simpson JA, Rossi AG, Haslett C, Sethi T |
| Journal | The American journal of pathology |
| Volume | 172 |
| Issue | 2 |
| Pagination | 395-405 |
| Date Published | 2008 Feb |
| ISSN | 0002-9440 |
| Keywords | Animals, Apoptosis, Flow Cytometry, Galectin 3, Humans, Macrophages, Mice, Mice, Mutant Strains, Neutrophil Activation, Neutrophils, Phagocytosis, Pneumonia, Pneumococcal, Streptococcus pneumoniae |
| Abstract | 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. |
| Alternate Journal | Am. J. Pathol. |
