A composite model of the human postcapillary venule for investigation of microvascular leukocyte recruitment
A composite model of the human postcapillary venule for investigation of microvascular leukocyte recruitment
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DOI：
10.1096/fj.13-240986
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发表时间：
2014-03-01
期刊：
影响因子：
4.8
通讯作者：
Gonzalez, Anjelica L.
中科院分区：
文献类型：
--
作者：
Lauridsen, Holly M.;Pober, Jordan S.;Gonzalez, Anjelica L.
神经元外渗发生在毛细血管后小静脉，即由内皮细胞（EC）、周细胞（PC）和基底膜（BM）组成的结构。我们构建了人毛细血管后微静脉的复合模型，将EC与PC或PC沉积的BM相结合，以更好地研究这一过程。静止和肿瘤坏死因子（TNF-α）激活的复合物显示钙粘蛋白、E-选择素、细胞间粘附分子1（ICAM-1）、血管细胞粘附分子1（VCAM-1）、血小板内皮细胞粘附分子1（PECAM-1）、CD 99和白细胞介素8（IL-8）的原位样表达。TNF-α激活后，内皮细胞比PC支持更大的中性粒细胞粘附（66.1%对23.7%的输入细胞）和迁移（35.1%对7.20%的输入细胞），但复合物在两种测定中表现为与内皮细胞相似（无显著差异）。TNF-激活的EC条件培养基（CM）增加了跨PC的迁移，而TNF-激活的PC-CM减少了跨EC的迁移，在PC衍生的BM上培养降低了与EC的粘附和跨EC的迁移。抗极晚期抗原4（VLA-4;中性粒细胞）抑制粘附TNF-激活的复合物，但不单独的EC。抗CD 99（在所有3种细胞类型上表达）抑制跨复合物（对照的14.5%）的迁移超过跨EC（对照的39.0%），并且小静脉剪切应力减少跨EC（静态的17.3%）的迁移超过跨复合物（静态的36.7%）。这些结果提供了我们的复合人EC/PC/BM微静脉构建体可以揭示炎症级联反应中新的相互作用的概念证据。M.，Pober，J.S.，冈萨雷斯，A. L.研究微血管白细胞募集的人毛细血管后微静脉复合模型。
Neutrophil extravasation occurs across postcapillary venules, structures composed of endothelial cells (ECs), pericytes (PCs), and basement membrane (BM). We constructed composite models of the human postcapillary venule, combining ECs with PCs or PC-deposited BM, to better study this process. Quiescent and tumor necrosis factor (TNF-)-activated composites demonstrated in situ-like expression of cadherins, E-selectin, intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), platelet-endothelial cell adhesion molecule 1 (PECAM-1), CD99, and interleukin 8 (IL-8). After TNF- activation, the ECs supported greater neutrophil adhesion (66.1 vs. 23.7% of input cells) and transmigration (35.1 vs. 7.20% of input cells) than did the PCs, but the composites behaved comparably (no significant difference) to ECs in both assays. TNF--activated EC-conditioned medium (CM) increased transmigration across the PCs, whereas TNF--activated PC-CM decreased transmigration across the ECs, and culturing on PC-derived BM decreased both adhesion to and transmigration across the ECs. Anti-very late antigen 4 (VLA-4; on neutrophils) inhibited adhesion to TNF--activated composites, but not to ECs alone. Anti-CD99 (expressed on all 3 cell types) inhibited transmigration across the composites (14.5% of control) more than across the ECs (39.0% of control), and venular shear stress reduced transmigration across the ECs (17.3% of static) more than across the composites (36.7% of static). These results provide proof of concept that our composite human EC/PC/BM venular construct can reveal new interactions in the inflammatory cascade.Lauridsen, H. M., Pober, J. S., Gonzalez, A. L. A composite model of the human postcapillary venule for investigation of microvascular leukocyte recruitment.