Regulation of endothelial cell adhesion molecule expression by mast cells, macrophages, and neutrophils.
Regulation of endothelial cell adhesion molecule expression by mast cells, macrophages, and neutrophils.
复制标题
DOI：
10.1371/journal.pone.0014525
复制
发表时间：
2011-01-14
期刊：
影响因子：
3.7
通讯作者：
Shi GP
中科院分区：
文献类型：
--
作者：
Zhang J;Alcaide P;Liu L;Sun J;He A;Luscinskas FW;Shi GP
白细胞粘附到血管内皮以及随后的跨内皮迁移在动脉粥样硬化等心血管疾病的发病机制中发挥着重要作用。白细胞粘附是通过炎性细胞因子的作用，通过内皮的局部激活来介导的。然而，激活内皮细胞的确切促炎因子及其细胞来源仍未完全确定。使用来自野生型、Tnf−/−、Ifng−/−、Il6−/− 小鼠的骨髓来源的肥大细胞，我们证明来自肥大细胞的所有三种促炎细胞因子均诱导小鼠心脏内皮细胞（MHEC）中血管细胞粘附分子-1（VCAM-1）、细胞间粘附分子-1（ICAM-1）、P-选择素和E-选择素在mRNA和蛋白质水平上的表达。与TNF-α和IL6相比，IFN-γ对mRNA水平的诱导作用较弱，但在蛋白质水平上，IL6和IFN-γ的诱导作用均弱于TNF-α。在生理剪切流条件下，肥大细胞来源的 TNF-α 和 IL6 在激活 MHEC 和促进中性粒细胞粘附方面比 IFN-γ 更有效。当使用嗜中性粒细胞或巨噬细胞时，也得到了类似的观察结果。中性粒细胞和巨噬细胞产生与肥大细胞相同的促炎细胞因子来诱导 MHEC 粘附分子表达，但巨噬细胞衍生的 IFN-γ 在诱导 MHEC 中 VCAM-1 表达方面的作用可以忽略不计。肥大细胞、中性粒细胞和巨噬细胞释放促炎细胞因子，例如 TNF-α、IFN-γ 和 IL6，诱导内皮细胞粘附分子的表达并招募白细胞，这对于血管炎症性疾病的发病机制至关重要。
Leukocyte adhesion to the vascular endothelium and subsequent transendothelial migration play essential roles in the pathogenesis of cardiovascular diseases such as atherosclerosis. The leukocyte adhesion is mediated by localized activation of the endothelium through the action of inflammatory cytokines. The exact proinflammatory factors, however, that activate the endothelium and their cellular sources remain incompletely defined. Using bone marrow-derived mast cells from wild-type, Tnf−/−, Ifng−/−, Il6−/− mice, we demonstrated that all three of these pro-inflammatory cytokines from mast cells induced the expression of vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), P-selectin, and E-selectin in murine heart endothelial cells (MHEC) at both mRNA and protein levels. Compared with TNF-α and IL6, IFN-γ appeared weaker in the induction of the mRNA levels, but at protein levels, both IL6 and IFN-γ were weaker inducers than TNF-α. Under physiological shear flow conditions, mast cell-derived TNF-α and IL6 were more potent than IFN-γ in activating MHEC and in promoting neutrophil adhesion. Similar observations were made when neutrophils or macrophages were used. Neutrophils and macrophages produced the same sets of pro-inflammatory cytokines as did mast cells to induce MHEC adhesion molecule expression, with the exception that macrophage-derived IFN-γ showed negligible effect in inducing VCAM-1 expression in MHEC. Mast cells, neutrophils, and macrophages release pro-inflammatory cytokines such as TNF-α, IFN-γ, and IL6 that induce expression of adhesion molecules in endothelium and recruit of leukocytes, which is essential to the pathogenesis of vascular inflammatory diseases.
登录
查看更多内容
影响因子：
6
作者：
Lim, YC;Garcia-Cardena, G;Luscinskas, FW
通讯作者：
Luscinskas, FW
影响因子：
37.8
作者：
Naruko, T;Ueda, M;Becker, AE
通讯作者：
Becker, AE
影响因子：
3.3
作者：
ATKINSON, JB;ROBINOWITZ, M;VIRMANI, R
通讯作者：
VIRMANI, R
影响因子：
14.2
作者：
de Vries, IJM;Langeveld-Wildschut, EG;Bruijnzeel-Koomen, CAFM
通讯作者：
Bruijnzeel-Koomen, CAFM
影响因子：
8.7
作者：
Nageh, MF;Sandberg, ET;Beaudet, AL
通讯作者：
Beaudet, AL