Farnworth Sarah L, Henderson Neil C, Mackinnon Alison C, Atkinson Kirsten M, Wilkinson Tom, Dhaliwal Kevin, Hayashi Katsutoshi, Simpson A John, Rossi Adriano G, Haslett Christopher, Sethi Tariq
Centre for Inflammation Research, The Queen's Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, UK.
Am J Pathol. 2008 Feb;172(2):395-405. doi: 10.2353/ajpath.2008.070870. Epub 2008 Jan 17.
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.
革兰氏阳性菌肺炎链球菌是全球社区获得性肺炎的主要病因，会导致高死亡率。我们的体内研究表明，与野生型小鼠相比，半乳糖凝集素-3(-/-)小鼠在感染肺炎链球菌后会发生更严重的肺炎，表现为菌血症增加和肺损伤加重，并且半乳糖凝集素-3部分通过增强中性粒细胞功能来降低肺炎球菌肺炎的严重程度。具体而言，我们发现：1）半乳糖凝集素-3直接作为中性粒细胞激活剂并增强fMLP的作用；2）外源性半乳糖凝集素-3增强中性粒细胞对细菌的吞噬作用并延迟中性粒细胞凋亡；3）与野生型相比，半乳糖凝集素-3(-/-)巨噬细胞对凋亡中性粒细胞的吞噬效率较低；4）半乳糖凝集素-3在体外对肺炎链球菌具有抑菌特性。此外，体内回补重组半乳糖凝集素-3可保护半乳糖凝集素-3缺陷小鼠不发生严重肺炎。总之，这些结果表明半乳糖凝集素-3是宿主抵御肺炎球菌感染的关键分子。旨在增强半乳糖凝集素-3活性的治疗策略可能既能增强炎症细胞功能（通过直接影响中性粒细胞反应性和延长中性粒细胞寿命），又具有直接抑菌活性，从而改善严重肺炎球菌感染后的临床结局。
