Couture Patrick, Paradis-Massie Jérémie, Oualha Nadia, Thibault Gaétan
Institut de recherches cliniques de Montréal, Université de Montréal, Montréal, Québec, Canada.
Exp Cell Res. 2009 Aug 1;315(13):2192-206. doi: 10.1016/j.yexcr.2009.04.013. Epub 2009 Apr 24.
During tissue inflammation, infiltrated leukocytes may have physical contacts with fibroblasts. We observed that neutrophils and B lymphocytes adhered in a larger proportion than T cells on cultured fibroblasts. Microscopy showed that adhesion was also characterized by leukocyte engulfment by the fibroblasts. In migration assays, only neutrophils and B lymphocytes were selectively able to migrate through a fibroblast barrier. Adhesion and migration were increased by stimulation with tumor necrosis factor-alpha (TNF-alpha) and phorbol-12-myristate-13-acetate (PMA). Antibodies against ICAM-1/beta2 integrin blocked the interaction of neutrophils to fibroblasts. For B lymphocytes the couple VCAM-1/alpha4 integrin was also involved in this interaction. Human skin fibroblasts presented similar adhesion characteristics as rat cardiac fibroblasts. By measuring the distance between the border of migration holes and cadherin-positive adherens junctions, more than 65% of the holes correspond to the transcellular route over the paracellular route. Furthermore, vimentin staining revealed that the migration holes were highly nested by intermediate filaments in accordance with the transcellular route. Our results demonstrated that engulfment of neutrophils and B lymphocytes by fibroblasts resulted in selective passage by a transcellular route.
在组织炎症期间，浸润的白细胞可能与成纤维细胞发生物理接触。我们观察到，在培养的成纤维细胞上，中性粒细胞和B淋巴细胞的黏附比例高于T细胞。显微镜检查显示，黏附的特征还包括成纤维细胞对白细胞的吞噬。在迁移试验中，只有中性粒细胞和B淋巴细胞能够选择性地穿过成纤维细胞屏障。用肿瘤坏死因子-α（TNF-α）和佛波醇-12-肉豆蔻酸酯-13-乙酸酯（PMA）刺激可增加黏附和迁移。抗ICAM-1/β2整合素抗体可阻断中性粒细胞与成纤维细胞的相互作用。对于B淋巴细胞，VCAM-1/α4整合素对也参与了这种相互作用。人皮肤成纤维细胞表现出与大鼠心脏成纤维细胞相似的黏附特性。通过测量迁移孔边界与钙黏蛋白阳性黏附连接之间的距离，超过65%的孔对应于跨细胞途径而非细胞旁途径。此外，波形蛋白染色显示，迁移孔被中间丝高度包裹，符合跨细胞途径。我们的结果表明，成纤维细胞对中性粒细胞和B淋巴细胞的吞噬导致了跨细胞途径的选择性通过。
