Nick J A, Avdi N J, Gerwins P, Johnson G L, Worthen G S
Department of Medicine and Division of Basic Sciences, National Jewish Center for Immunology and Respiratory Medicine, Denver, CO 80206, USA.
J Immunol. 1996 Jun 15;156(12):4867-75.
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.
脂多糖（LPS）刺激人中性粒细胞是脓毒症和成人呼吸窘迫综合征发病机制的核心。中性粒细胞在LPS刺激后引发细胞反应的细胞内信号通路尚不清楚。我们报告，中性粒细胞暴露于LPS会导致p38丝裂原活化蛋白（MAP）激酶磷酸化并激活，呈浓度依赖性，在20至25分钟时反应最大。通过离子交换色谱法对p38 MAP激酶进行部分纯化，确定其与p42/p44（细胞外信号调节激酶（ERK-1和ERK-2）MAP激酶）不同。LPS在人中性粒细胞中激活p38 MAP激酶是通过CD14（一种假定的LPS受体）实现的，并且需要含有LPS结合蛋白的血浆存在。这种细胞内信号通路独立于蛋白激酶C，不涉及Raf、MAP/ERK激酶激酶-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 N端激酶的激活。
