Oxidative burst of circulating neutrophils following traumatic brain injury in human.
Oxidative burst of circulating neutrophils following traumatic brain injury in human.
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DOI：
10.1371/journal.pone.0068963
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Zhang Z
中科院分区：
文献类型：
--
作者：
Liao Y;Liu P;Guo F;Zhang ZY;Zhang Z
除了损伤部位的继发性损伤外，创伤性脑损伤（TBI）还可引起全身性炎症反应，这可能会对最初未受影响的器官造成损伤，并可能进一步加重原始损伤。在这里，我们调查了血浆中的重要炎症介质的水平，循环白细胞的氧化活性，特别是关注中性粒细胞，从TBI受试者和对照受试者一般创伤6小时至2周后受伤，与未受伤的受试者的值相比。我们观察到TBI患者血浆炎症细胞因子/分子TNF-α、IL-6和CRP水平升高，循环白细胞计数显著增加，循环白细胞中TNF-α和iNOS表达升高，这表明TBI后存在全身炎症反应。我们的数据进一步显示，白细胞匀浆中自由基的产生增加，循环白细胞中关键氧化酶iNOS、考克斯-2和NADPH氧化酶（gp 91 phox）的表达升高，表明TBI后强烈诱导氧化爆发，其显著高于一般创伤对照受试者。此外，流式细胞术测定证明中性粒细胞是TBI后循环中最大的群体，并显示脑创伤后循环中性粒细胞的氧化活性显著上调和吞噬率抑制。提示高度活化的中性粒细胞可能在脑损伤后继发性损害中起重要作用，即使在脑损伤外也是如此。总之，TBI诱导的强全身炎症反应，特别是循环白细胞（主要是中性粒细胞）的氧化活性的强烈增加，可导致全身损伤、旁观者组织/器官的功能障碍/损伤，甚至进一步加剧继发性局部损伤。控制这些病理生理过程可能是一种有前途的治疗策略，并将保护未受影响的器官和受损的大脑免受继发性损害。
Besides secondary injury at the lesional site, Traumatic brain injury (TBI) can cause a systemic inflammatory response, which may cause damage to initially unaffected organs and potentially further exacerbate the original injury. Here we investigated plasma levels of important inflammatory mediators, oxidative activity of circulating leukocytes, particularly focusing on neutrophils, from TBI subjects and control subjects with general trauma from 6 hours to 2 weeks following injury, comparing with values from uninjured subjects. We observed increased plasma level of inflammatory cytokines/molecules TNF-α, IL-6 and CRP, dramatically increased circulating leukocyte counts and elevated expression of TNF-α and iNOS in circulating leukocytes from TBI patients, which suggests a systemic inflammatory response following TBI. Our data further showed increased free radical production in leukocyte homogenates and elevated expression of key oxidative enzymes iNOS, COX-2 and NADPH oxidase (gp91phox) in circulating leukocytes, indicating an intense induction of oxidative burst following TBI, which is significantly greater than that in control subjects with general trauma. Furthermore, flow cytometry assay proved neutrophils as the largest population in circulation after TBI and showed significantly up-regulated oxidative activity and suppressed phagocytosis rate for circulating neutrophils following brain trauma. It suggests that the highly activated neutrophils might play an important role in the secondary damage, even outside the injured brain. Taken together, the potent systemic inflammatory response induced by TBI, especially the intensively increase oxidative activity of circulating leukocytes, mainly neutrophils, may lead to a systemic damage, dysfunction/damage of bystander tissues/organs and even further exacerbate secondary local damage. Controlling these pathophysiological processes may be a promising therapeutic strategy and will protect unaffected organs and the injured brain from the secondary damage.
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DOI：
10.1016/j.injury.2007.10.003
发表时间：
2007-12-01
影响因子：
2.5
作者：
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