Histamine and thrombin modulate endothelial focal adhesion through centripetal and centrifugal forces

Histamine and thrombin modulate endothelial focal adhesion through centripetal and centrifugal forces
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DOI:
10.1172/jci118493
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发表时间:
1996-02-15
影响因子:
15.9
通讯作者:
Shasby, DM
Shasby, DM
中科院分区:
医学1区
文献类型:
--
作者:
Moy, AB;VanEngelenhoven, J;Shasby, DM

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我们研究了肌动蛋白-肌球蛋白收缩在组胺和凝血酶引起的人脐静脉内皮细胞局灶性黏附调节中的作用。焦点粘附性是通过在微电极上生长的培养单分子层的电阻来测量的。肌动蛋白-肌球蛋白收缩测量为生长在胶原凝胶上的培养单层的等长张力。组胺立即降低电阻,但在3-5分钟内恢复到基础水平。组胺不增加等长张力。凝血酶也立即降低阻力,但阻力在40-60分钟内不会恢复到基础水平。凝血酶也增加了等长张力。肌球蛋白轻链激酶的抑制剂ML-7可防止肌球蛋白轻链磷酸化增加和凝血酶作用下细胞张力的增加。ML-7不能阻止暴露于凝血酶的细胞的电阻下降。相反,与单独暴露于凝血酶的细胞相比,ML-7在更短的时间内(20分钟)将电阻恢复到基础水平。还有。组胺随后增加了对基础水平以上的电阻。而凝血酶在最大张力形成期间引起阻力增加。因此,组胺和凝血酶通过向心力和离心力调节内皮细胞的局部黏附。
We examined the contribution of actin-myosin contraction to the modulation of human umbilical vein endothelial cell focal adhesion caused by histamine and thrombin. Focal adhesion was measured as the electrical resistance across a cultured monolayer grown on a microelectrode. Actin-myosin contraction was measured as isometric tension of cultured monolayers grown on a collagen gel. Histamine immediately decreased electrical resistance but returned to basal levels within 3-5 min. Histamine did not increase isometric tension. Thrombin also immediately decreased electrical resistance, but, however, resistance did not return to basal levels for 40-60 min. Thrombin also increased isometric tension. ML-7, an inhibitor of myosin light chain kinase, prevented increases in myosin light chain phosphorylation and increases in tension development in cells exposed to thrombin. ML-7 did not prevent a decline in electrical resistance in cells exposed to thrombin. instead, ML-7 restored the electrical resistance to basal levels in a shorter period of time (20 min) than cells exposed to thrombin alone. Also. histamine subsequently increased electrical resistance to above basal levels. and thrombin initiated an increase in resistance during the time of peak tension development. Hence, histamine and thrombin modulate endothelial cell focal adhesion through centripetal and centrifugal forces.