Hypertonicity regulates the function of human neutrophils by modulating chemoattractant receptor signaling and activating mitogen-activated protein kinase p38

被引:136
作者
Junger, WG
Hoyt, DB
Davis, RE
Herdon-Remelius, C
Namiki, S
Junger, H
Loomis, W
Altman, A
机构
[1] Univ Calif San Diego, Trauma Res Lab 8236, Dept Surg, Div Trauma, San Diego, CA 92103 USA
[2] La Jolla Inst Allergy & Immunol, San Diego, CA 92121 USA
关键词
hypertonic saline resuscitation; neutrophil activation and function; inflammation; signaling; MAP kinase;
D O I
10.1172/JCI1354
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
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.
引用
收藏
页码:2768 / 2779
页数:12
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