Department of Pediatrics, Harvard Medical School, Boston, MA 02115, United States; Center for Immunology and Inflammatory Diseases and the Food Allergy Center, Massachusetts General Hospital, Charlestown, MA 02129, United States.
Center for Immunology and Inflammatory Diseases and the Food Allergy Center, Massachusetts General Hospital, Charlestown, MA 02129, United States.
Prostaglandins Other Lipid Mediat. 2014 Jan;108:1-8. doi: 10.1016/j.prostaglandins.2013.11.001. Epub 2013 Dec 4.
Pathogen induced migration of neutrophils across mucosal epithelial barriers requires epithelial production of the chemotactic lipid mediator, hepoxilin A3 (HXA3). HXA3 is an eicosanoid derived from arachidonic acid. Although eosinophils are also capable of penetrating mucosal surfaces, eosinophilic infiltration occurs mainly during allergic processes whereas neutrophils dominate mucosal infection. Both neutrophils and eosinophils can respond to chemotactic gradients of certain eicosanoids, however, it is not known whether eosinophils respond to pathogen induced lipid mediators such as HXA3. In this study, neutrophils and eosinophils were isolated from human blood and placed on the basolateral side of polarized epithelial monolayers grown on permeable Transwell filters and challenged by various chemotactic gradients of distinct lipid mediators. We observed that both cell populations migrated across epithelial monolayers in response to a leukotriene B4 (LTB4) gradient, whereas only eosinophils migrated toward a prostaglandin D2 (PGD2) gradient. Interestingly, while pathogen induced neutrophil trans-epithelial migration was substantial, pathogen induced eosinophil trans-epithelial migration was not observed. Further, gradients of chemotactic lipids derived from pathogen infected epithelial cells known to be enriched for HXA3 as well as purified HXA3 drove significant numbers of neutrophils across epithelial barriers, whereas eosinophils failed to respond to these gradients. These data suggest that although the eicosanoid HXA3 serves as an important neutrophil chemo-attractant at mucosal surfaces during pathogenic infection, HXA3 does not appear to exhibit chemotactic activity toward eosinophils.
病原体诱导的中性粒细胞穿过黏膜上皮屏障的迁移需要上皮细胞产生趋化性脂质介质，即 hepoxilin A3 (HXA3)。HXA3 是一种源自花生四烯酸的类二十烷酸。尽管嗜酸性粒细胞也能够穿透黏膜表面，但嗜酸性粒细胞浸润主要发生在过敏过程中，而中性粒细胞则主导黏膜感染。中性粒细胞和嗜酸性粒细胞都可以对某些类二十烷酸的趋化性梯度做出反应，但是否嗜酸性粒细胞可以对病原体诱导的脂质介质（如 HXA3）做出反应尚不清楚。在这项研究中，我们从人血液中分离出中性粒细胞和嗜酸性粒细胞，将其放置在极化上皮单层细胞的基底外侧，并将其置于不同趋化性脂质介质的趋化性梯度下进行挑战。我们观察到，两种细胞群都可以响应白三烯 B4 (LTB4) 梯度穿过上皮单层细胞，而只有嗜酸性粒细胞可以响应前列腺素 D2 (PGD2) 梯度。有趣的是，虽然病原体诱导的中性粒细胞跨上皮迁移很明显，但未观察到病原体诱导的嗜酸性粒细胞跨上皮迁移。此外，来自受病原体感染的上皮细胞的趋化性脂质的梯度，已知这些细胞富含 HXA3 以及纯化的 HXA3，可驱动大量中性粒细胞穿过上皮屏障，而嗜酸性粒细胞则无法对这些梯度做出反应。这些数据表明，尽管类二十烷酸 HXA3 在致病性感染期间作为黏膜表面的重要中性粒细胞趋化因子，但 HXA3 似乎对嗜酸性粒细胞没有趋化活性。
