LYSOZYME, A MEDIATOR OF SEPSIS THAT DEPOSITS IN THE SYSTEMIC VASCULATURE AND KIDNEY AS A POSSIBLE MECHANISM OF ACUTE ORGAN DYSFUNCTION
LYSOZYME, A MEDIATOR OF SEPSIS THAT DEPOSITS IN THE SYSTEMIC VASCULATURE AND KIDNEY AS A POSSIBLE MECHANISM OF ACUTE ORGAN DYSFUNCTION
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DOI：
10.1097/shk.0000000000000095
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发表时间：
2014-03-01
期刊：
影响因子：
3.1
通讯作者：
Mink, Steven N.
中科院分区：
文献类型：
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作者：
Gotes, Jose;Kasian, Krika;Mink, Steven N.
在脓毒性休克（SS）中，许多器官系统的功能障碍在疾病过程中发展，尽管机制尚不清楚。在早期的研究中，我们报道了溶菌酶-C（Lzm-S），一种从白细胞和巨噬细胞释放的蛋白质，是铜绿假单胞菌SS犬模型中心肌抑制和血管舒张的介导剂。尽管Lzm-S的这两种作用都依赖于其内在产生过氧化氢的能力，但我们随后表明，在该模型中，Lzm-S也可以存款在体循环动脉的血管平滑肌层内。在本研究中，我们扩展了我们以前的研究结果。我们使用犬颈动脉器官浴制备来研究血管平滑肌层内Lzm-S沉积的时间过程和剂量依赖性。我们使用人主动脉血管平滑肌细胞制备物来确定Lzm-S是否可以持续抑制该制备物的收缩。我们还使用犬铜绿假单胞菌模型来确定Lzm-S沉积是否可能发生在其他器官中，例如肾脏、肝脏和小肠。结果表明，在颈动脉器官浴制备中，Lzm-S在滴注后数分钟内发生沉积，并且存在剂量反应效应。在人主动脉血管平滑肌细胞制备中，Lzm-S在4天期间抑制收缩。在体内模型中，Lzm-S在肾脏和上级肠系膜动脉中蓄积。在犬肾上皮制备中，我们进一步表明Lzm-S可以被肾小管吸收以激活炎症途径。我们的结论是，Lzm-S可以存款在全身血管和肾脏SS，这种沉积可能会导致急性器官功能障碍。
In septic shock (SS), dysfunction of many organ systems develops during the course of the illness, although the mechanisms are not clear. In earlier studies, we reported that lysozyme-c (Lzm-S), a protein that is released from leukocytes and macrophages, was a mediator of the myocardial depression and vasodilation that develop in a canine model of Pseudomonas aeruginosa SS. Whereas both of these effects of Lzm-S are dependent on its ability to intrinsically generate hydrogen peroxide, we subsequently showed that Lzm-S can also deposit within the vascular smooth muscle layer of the systemic arteries in this model. In the present study, we extend our previous findings. We used a canine carotid artery organ bath preparation to study the time course and dose dependence of Lzm-S deposition within the vascular smooth muscle layer. We used a human aortic vascular smooth muscle cell preparation to determine whether Lzm-S can persistently inhibit contraction in this preparation. We also used a canine P. aeruginosa model to determine whether Lzm-S deposition might occur in other organs such as the kidney, liver, and small intestine. The results showed that, in the carotid artery organ bath preparation, Lzm-S deposition occurred within minutes of instillation and there was a dose-response effect. In the human aortic vascular smooth muscle cell preparation, Lzm-S inhibited contraction during a 4-day period. In the in vivo model, Lzm-S accumulated in the kidney and the superior mesenteric artery. In a canine renal epithelial preparation, we further showed that Lzm-S can be taken up by the renal tubules to activate inflammatory pathways. We conclude that Lzm-S can deposit in the systemic vasculature and kidneys in SS, where this deposition could lead to acute organ dysfunction.