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- W1859771235 abstract "Neutrophils are the first leukocyte population to be recruited from the circulation following tissue injury or infection, where they play key roles in host defense. However, recent evidence indicates recruited neutrophils can also enter lymph and shape adaptive immune responses downstream in draining lymph nodes. At present, the cellular mechanisms regulating neutrophil entry to lymphatic vessels and migration to lymph nodes are largely unknown. Here, we have investigated these events in an in vivo mouse Mycobacterium bovis bacillus Calmette-Guérin vaccination model, ex vivo mouse dermal explants, and in vitro Transwell system comprising monolayers of primary human dermal lymphatic endothelial cells. We demonstrate that neutrophils are reliant on endothelial activation for adhesion, initially via E-selectin and subsequently, by integrin-mediated binding to ICAM-1 and VCAM-1, combined with CXCL8-dependent chemotaxis. Moreover, we reveal that integrin-mediated neutrophil adhesion plays a pivotal role in subsequent transmigration by focusing the action of matrix metalloproteinases and the 15-lipoxygenase-1-derived chemorepellent 12(S)-hydroxyeicosatetraenoic acid at neutrophil:endothelial contact sites to induce transient endothelial junctional retraction and rapid, selective neutrophil trafficking. These findings reveal an unexpectedly intimate collaboration between neutrophils and the lymphatic vessel endothelium, in which these phagocytic leukocytes act as pathfinders for their own transit during inflammation." @default.
- W1859771235 created "2016-06-24" @default.
- W1859771235 creator A5007070612 @default.
- W1859771235 creator A5030823404 @default.
- W1859771235 creator A5062882861 @default.
- W1859771235 creator A5065928472 @default.
- W1859771235 date "2015-07-27" @default.
- W1859771235 modified "2023-10-15" @default.
- W1859771235 title "Neutrophils rapidly transit inflamed lymphatic vessel endothelium via integrin-dependent proteolysis and lipoxin-induced junctional retraction" @default.
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- W1859771235 doi "https://doi.org/10.1189/jlb.1hi0415-149r" @default.
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- W1859771235 hasPublicationYear "2015" @default.
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