Common and distinct intracellular signaling pathways in human neutrophils utilized by platelet activating factor and FMLP
Common and distinct intracellular signaling pathways in human neutrophils utilized by platelet activating factor and FMLP
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DOI：
10.1172/jci119263
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发表时间：
1997-03-01
影响因子：
15.9
通讯作者：
Worthen, GS
中科院分区：
文献类型：
--
作者：
Nick, JA;Avdi, NJ;Worthen, GS
化学诱导剂FMLP或血小板激活因子(PAF)刺激人中性粒细胞产生不同但重叠的功能反应。我们质疑这些差异是否可能反映了细胞内信号转导的模式。PAF或FMLP刺激可导致与HOG-1(P38)MAPK同源的38-kD小鼠MAPK同源物的等量磷酸化和激活。FMLP和PAF均不激活c-Jun氨基末端MAPK(JNKs)。在相同条件下，FMLP能显著激活p42/44(ERK)MAPK，而PAF不能。FMLP和PAF均激活已知的p38MAPK激活剂--MKK3。MAP ERK激酶-1(MEKK1)和Raf均被FMLP强烈激活，但被PAF激活最小。百日咳毒素可阻断FMLP诱导的p42/44(ERK)MAPK通路的激活，但不能阻断p38MAPK的激活。一种特异性的p38MAPK抑制剂(SK&F 86002)可抑制FMLP反应中超氧阴离子的产生，并降低对PAF或FMLP的黏附和趋化作用。这些结果显示了两种化学诱导剂的不同的细胞内信号模式，并表明细胞内信号级联的选择性激活可能是不同的功能反应模式的基础。
Stimulation of human neutrophils with chemoattractants FMLP or platelet activating factor (PAF) results in different but overlapping functional responses. We questioned whether these differences might reflect patterns of intracellular signal transduction. Stimulation with either PAF or FMLP resulted in equivalent phosphorylation and activation of the mitogen-activated protein kinase (MAPk) homologue 38-kD murine MAP kinase homologous to HOG-1 (p38) MAPk. Neither FMLP nor PAF activated c-jun NH2-terminal MAPk (JNKs). Under identical conditions, FMLP but not PAF, resulted in significant p42/44 (ERK) MAPk activation. Both FMLP and PAF activated MAP kinase kinase-3 (MKK3), a known activator of p38 MAPk. Both MAP ERK kinase kinase-1 (MEKK1) and Raf are activated strongly by FMLP, but minimally by PAF. Pertussis toxin blocked FMLP-induced activation of the p42/44 (ERK) MAPk cascade, but not that of p38 MAPk. A specific p38 MAPk inhibitor (SK&F 86002) blocked superoxide anion production in response to FMLP and reduced adhesion and chemotaxis in response to PAF or FMLP. These results demonstrate distinct patterns of intracellular signaling for two chemoattractants and suggest that selective activation of intracellular signaling cascades may underlie different patterns of functional responses.