Hyperosmolarity attenuates TNF-α-mediated proinflammatory activation of human pulmonary microvascular endothelial cells.
Hyperosmolarity attenuates TNF-α-mediated proinflammatory activation of human pulmonary microvascular endothelial cells.
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DOI：
10.1097/shk.0b013e3182894016
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发表时间：
2013-04
期刊：
影响因子：
--
通讯作者：
Silliman CC
中科院分区：
文献类型：
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作者：
Banerjee A;Moore EE;McLaughlin NJ;Lee L;Jones WL;Johnson JL;Nydam TL;Silliman CC
中性粒细胞（PMN）-内皮细胞（EC）粘附对于急性肺损伤中观察到的PMN介导的过度炎症至关重要。高渗盐水（HTS）用于失血性休克复苏与PMN介导的肺损伤/急性呼吸窘迫综合征的发生率降低有关。我们假设生理上可接受的高渗孵育（170 mM vs. 140 mM，渗透压范围为360-300 mOsm/L）抑制人肺微血管内皮细胞（HMVEC）的促炎活化。在等渗（对照）和高渗条件下，研究了HMVECs对TNFα的促炎性激活，包括IL-8释放、ICAM-1表面表达、PMN粘附和信号传导机制。单独的高渗透压对基础IL-8释放或ICAM-1表面表达没有影响，但确实导致TNFα诱导的IL-8释放、ICAM-1表面表达和PMN：HMVEC粘附的浓度依赖性降低。相反，HTS激活p38丝裂原活化蛋白激酶（MAPK），并增强TNFα激活p38 MAPK。尽管有这种基础激活，高渗孵育减弱了TNFα刺激的IL-8释放和ICAM-1表面表达以及随后的PMN粘附，而p38 MAPK抑制没有进一步影响高渗条件对ICAM-1表面表达的影响。此外，TNFα诱导NF-κ B DNA结合，但HTS条件使其减弱31%（p<0.01）。总之，HTS通过减弱NF-kB信号传导减少PMN：HMVEC粘附以及TNFα诱导的原代HMVEC的促炎性激活。
Firm neutrophil (PMN)-endothelial (EC) adhesion is crucial to the PMN-mediated hyperinflammation observed in acute lung injury. Hypertonic saline (HTS) used for resuscitation of hemorrhagic shock has been associated with a decreased incidence of PMN-mediated lung injury/acute respiratory distress syndrome. We hypothesize that physiologically accessible hypertonic incubation (170mM vs. 140mM, osmolarity ranging from 360-300 mOsm/L) inhibits pro-inflammatory activation of human pulmonary microvascular endothelial cells (HMVECs). Pro-inflammatory activation of HMVECs was investigated in response to TNFα including IL-8 release, ICAM-1 surface expression, PMN adhesion, and signaling mechanisms under both isotonic (control) and hypertonic conditions. Hyperosmolarity alone had no effect on either basal IL-8 release or ICAM-1 surface expression, but did lead to concentration-dependent decreases in TNFα–induced IL-8 release, ICAM-1 surface expression, and PMN:HMVEC adhesion. Conversely, HTS activated p38 mitogen-activated protein kinase (MAPK) and enhanced TNFα activation of p38 MAPK. Despite this basal activation, hyperosmolar incubation attenuated TNFα stimulated IL-8 release and ICAM-1 surface expression and subsequent PMN adherence, while p38 MAPK inhibition did not further influence the effects of hyperosmolar conditions on ICAM-1 surface expression. In addition, TNFα induced NF-kB DNA binding, but HTS conditions attenuated this by 31% (p<0.01). In conclusion, HTS reduces PMN:HMVEC adhesion as well as TNFα-induced pro-inflammatory activation of primary HMVECs via attenuation of NF-kB signaling.