Marmon Shana, Cammer Michael, Raine Cedric S, Lisanti Michael P
Exp Dermatol. 2009 Jan;18(1):88-90. doi: 10.1111/j.1600-0625.2008.00796.x. Epub 2008 Nov 19.
Neutrophil extravasation is central to inflammatory skin diseases like psoriasis and atopic dermatitis. In vivo, neutrophils have been shown to migrate through cell-to-cell junctions (paracellular pathway) or directly through the body of the endothelial cell (transcellular pathway). In vitro, however, neutrophil migration is a largely paracellular process where cells preferentially cross at tricellular corners devoid of tight junctions. To approximate the type of cells encountered by extravasating neutrophils in vivo, we developed a neutrophil-migration assay using primary human dermal microvascular endothelial cells. We show here that a large proportion of migrating neutrophils traverse a monolayer of microvascular endothelium using a purely transcellular pathway. In addition, we demonstrate that F-actin is rearranged similarly in neutrophils undergoing diapedesis along either route. This in vitro model closely simulates the physiological process of neutrophil extravasation in vivo and can be further utilized to evaluate the relative contribution of distinct migratory pathways to the pathophysiology of inflammatory skin disease.
中性粒细胞外渗是银屑病和特应性皮炎等炎症性皮肤病的核心环节。在体内，中性粒细胞已被证明可通过细胞间连接（旁细胞途径）或直接穿过内皮细胞体（穿细胞途径）迁移。然而，在体外，中性粒细胞迁移主要是一个旁细胞过程，细胞优先在没有紧密连接的三细胞角处穿过。为了模拟体内外渗中性粒细胞遇到的细胞类型，我们使用原代人真皮微血管内皮细胞开发了一种中性粒细胞迁移试验。我们在此表明，很大一部分迁移的中性粒细胞通过纯穿细胞途径穿过微血管内皮单层。此外，我们证明，沿任一途径进行跨内皮迁移的中性粒细胞中，F-肌动蛋白的重排方式相似。这种体外模型紧密模拟了体内中性粒细胞外渗的生理过程，可进一步用于评估不同迁移途径对炎症性皮肤病病理生理学的相对贡献。
