Activation of a p38 mitogen-activated protein kinase in human neutrophils by lipopolysaccharide.
Activation of a p38 mitogen-activated protein kinase in human neutrophils by lipopolysaccharide.
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DOI：
10.4049/jimmunol.156.12.4867
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发表时间：
1996-06
影响因子：
4.4
通讯作者：
J. Nick;N. Avdi;P. Gerwins;G. Johnson;G. Johnson;G. Worthen;G. Worthen
中科院分区：
文献类型：
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作者：
J. Nick;N. Avdi;P. Gerwins;G. Johnson;G. Johnson;G. Worthen;G. Worthen
内毒素对人中性粒细胞的刺激是败血症和成人呼吸窘迫综合征发病机制的核心。导致中性粒细胞内毒素刺激后细胞反应的细胞内信号通路尚不清楚。我们报道，中性粒细胞暴露于脂多糖导致p38丝裂原激活蛋白(MAP)激酶的磷酸化和激活，以浓度依赖的方式发生，最大反应时间为20-25分钟。通过离子交换层析对p38MAP的部分纯化，证实其不同于P42/P44(细胞外信号调节激酶(ERK-1和ERK-2)MAP激酶)。在中性粒细胞中，内毒素激活p38MAP激酶是通过CD14，一种建议的内毒素受体，并且需要含有内毒素结合蛋白的血浆的存在。这种细胞内信号通路不依赖于蛋白激酶C，不涉及Raf、MAP/ERK激酶-1、MAP/ERK激酶-1或MAP/ERK激酶-2，也不会导致p42/p44 ERK MAP激酶或c-jun氨基末端激酶的激活。
Stimulation of human neutrophils by LPS is central to the pathogenesis of sepsis and the adult respiratory distress syndrome. The intracellular signaling pathway that results in cellular responses following LPS stimulation in neutrophils is unknown. We report that exposure of neutrophils to LPS results in the phosphorylation and activation of a p38 mitogen-activated protein (MAP) kinase, occurring in a concentration-dependent manner, with maximum response at 20 to 25 min. Partial purification of a p38 MAP kinase by ion exchange chromatography established it as distinct from the p42/p44 (extracellular signal-regulated kinases (ERK-1 and ERK-2) MAP kinases). Activation of the p38 MAP kinase by LPS in human neutrophils occurs via CD14, a proposed LPS receptor, and requires the presence of plasma containing the LPS-binding protein. This intracellular signaling pathway is independent of protein kinase C and does not involve Raf, MAP/ERK kinase kinase-1, MAP/ERK kinase-1, or MAP/ERK kinase-2 and does not result in the activation of the p42/p44 ERK MAP kinases or the c-jun N-terminal kinases.