Complement depletion enhances pulmonary inflammatory response after liver injury
Complement depletion enhances pulmonary inflammatory response after liver injury
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DOI：
10.1016/j.gassur.2005.06.033
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发表时间：
2006-03-01
影响因子：
3.2
通讯作者：
Chapman, WC
中科院分区：
文献类型：
--
作者：
Glasgow, SC;Kanakasabai, S;Chapman, WC
肝脏冷冻消融术可产生急性肺损伤，伴随残余肝脏和肺中核因子（NF）-κ B的活化、C-X-C趋化因子的产生以及肺中性粒细胞浸润。活化的补体刺激枯否细胞分泌NF-κ B和细胞因子。使用HLL转基因小鼠（5' HIV-LTR-荧光素酶基因; 5' HIV-LTR是NF-κ B依赖性启动子）检查补体在冷冻消融后急性肺损伤发展中的作用。通过术前给予眼镜蛇毒因子（CVF）实现完全补体耗竭。肝脏冷冻消融后，对照组（119，093 +/-22，808净RLU/mg蛋白）和CVF治疗组小鼠（117，722 +/-14，932）的未消融肝脏残留物中的生物发光NF-κ B活性从累积基线（657 +/- 90，P < 0.0001）增加4小时。在肺中，补体耗竭诱导NF-κ B活化在早期和晚期均显著增加。同样地，相对于对照组，补体耗尽小鼠中的趋化因子更高（KC：493 +/-43vs269 +/-29pg/mg蛋白，P < 0.001; MIP-2：171 +/-29vs64 +/-13pg/mg蛋白，P < 0.0001）。肺髓过氧化物酶活性在24小时时相当，但补体耗竭导致中性粒细胞显著更快流入。补体耗竭通过NF-κ B活性的相对上调导致肝脏冷冻损伤后肺部炎症增加。活化的补体不是全身炎症反应的起始物;事实上，补体级联的下游组分可以减少随后的炎症。
Hepatic cryoablation can produce acute lung injury, with activation of nuclear factor (NF)-kappa B in the remnant liver and lungs, production of C-X-C chemokines, and neutropbil infiltration of the lungs. Activated complement stimulates NF-kappa B and cytokine secretion from Kupffer cells. The role of complement in the development of acute lung injury after cryoablation was examined using HLL transgenic mice (5' HIV-LTR-Luciferase gene; 5' HIV-LTR is an NF-kappa B-dependent promoter). Total complement depletion was achieved with preoperative administration of cobra venom factor (CVF). After hepatic cryoablation, bioluminescent NF-kappa B activity increased in the nonablated liver remnant by 4 hours in both control (119,093 +/- 22,808 net RLU/mg protein) and CVF-treated mice (117,722 +/- 14,932) from cumulative baseline (657 +/- 90, P < 0.0001). In the lung, complement-depletion induced significantly greater increases in NF-kappa B activation at both early and later times. Likewise, chemokines were higher in complement-depleted mice relative to controls (KC: 493 +/- 43 versus 269 +/- 29 pg/mg protein, P < 0.001; MIP-2: 171 +/- 29 versus 64 +/- 13 pg/mg protein, P < 0.0001). Pulmonary myeloperoxidase activity was equivalent at 24 hours, but complement-depletion caused a significantly more rapid influx of neutrophils. Complement depletion results in increased pulmonary inflammation following liver cryo injury via relative upregulation of NF-kappa B activity. Activated complement is not the initiator of the systemic inflammatory response; in fact, downstream components of the complement cascade may diminish subsequent inflammation.