Hypertonicity regulates the function of human neutrophils by modulating chemoattractant receptor signaling and activating mitogen-activated protein kinase p38
Hypertonicity regulates the function of human neutrophils by modulating chemoattractant receptor signaling and activating mitogen-activated protein kinase p38
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DOI：
10.1172/jci1354
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发表时间：
1998-06-15
影响因子：
15.9
通讯作者：
Altman, A
中科院分区：
文献类型：
--
作者：
Junger, WG;Hoyt, DB;Altman, A
过度的中性粒细胞激活会引起创伤后并发症，这可能会通过高渗盐水（IIS）复苏来减少。我们测试了这是否是因为HS调节了中性粒细胞功能。临床相关的高渗（10-25 mM）抑制脱粒和超氧化物的形成响应fMLP和阻断有丝分裂原活化蛋白激酶（MAPK）ERK 1/2和p38的激活，但不影响Ca 2+动员。HS不抑制响应于佛波酯肉豆蔻酸酯（PMA）的氧化爆发。这表明HS通过阻断PKC上游或远离PKC的信号通路来抑制中性粒细胞功能。HS本身激活p38，并增强对PKC激活的脱粒反应。这种增强被SB 203580抑制p38降低，表明p38上调参与NS诱导的脱粒增强。HS对先前用fMLP刺激的细胞的脱颗粒具有类似的作用，但其本身没有影响，这表明HS对脱颗粒的增强需要另一种信号。我们的结论是，依赖于其他刺激，WS可以抑制中性粒细胞激活通过拦截多个受体信号或增加脱粒通过增强p38信号。在患者中，HS复苏可以通过防止再灌注期间释放的趋化因子引起的中性粒细胞活化来减少创伤后并发症。
Excessive neutrophil activation causes posttraumatic complications, which may be reduced with hypertonic saline (IIS) resuscitation, We tested if this is because of modulated neutrophil function by HS. Clinically relevant hypertonicity (10-25 mM) suppressed degranulation and superoxide formation in response to fMLP and blocked the activation of the mitogen activated protein kinases (MAPK) ERK1/2 and p38, but did not affect Ca2+ mobilization. HS did not suppress oxidative burst in response to phorbol myristate acetate (PMA). This indicates that HS suppresses neutrophil function by intercepting signal pathways upstream of or apart from PKC. HS activated p38 by itself and enhanced degranulation in response to PKC activation. This enhancement was reduced by inhibition of p38 with SB203580, suggesting that p38 up-regulation participates in NS-induced enhancements of degranulation. HS had similar effects on the degranulation of cells that were previously stimulated with fMLP, but had no effect on its own, suggesting that HS enhancement of degranulation requires another signal. We conclude that depending on other stimuli, WS can suppress neutrophil activation by intercepting multiple receptor signals or augment degranulation by enhancing p38 signaling. In patients HS resuscitation may reduce posttraumatic complications by preventing neutrophil activation via chemotactic factors released during reperfusion.