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Different pathways leading to activation of extracellular signal-regulated kinase and p38 MAP kinase by formyl-methionyl-leucyl-phenylalanine or platelet activating factor in human neutrophils

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Journal of Biomedical Science

Summary

The signaling pathways leading to extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (MAPK) activation by N-formyl-Met-Leu-Phe (fMLP) or platelet activating factor (PAF) in human neutrophils were examined. Previously, we found that changes of intracellular Ca2+ ([Ca\(^{2+}]_{\rm i}\)) stimulated by PAF and fMLP were due to Ca2+ influx and internal Ca2+ release, respectively. To further determine the mechanism of MAPK activation and its relation with Ca2+ influx, blood from healthy human volunteers was taken by venous puncture. Human polymorphonuclear cells (PMNs) were isolated and incubated with protein kinase C (PKC) inhibitor Calphostin C, PKC-γ isoform inhibitor GF109203X, phosphatidylinositol 3-kinase (PI3K) inhibitors wortmannin and LY294002, phospholipase C (PLC) inhibitor U73122, phospholipase A2 (PLA2) inhibitor Aristolochic acid, store-operated calcium (SOC) channel inhibitor SKF96365, or extracellular calcium chelator EGTA followed by fMLP or PAF treatment. Phosphorylation of ERK p38 was determined by immunoblotting analysis. Our data indicate that neutrophil MAPK signaling pathways mediated by fMLP and PAF are different. PAF-induced ERK phosphorylation is mediated by PI3K, PKC, PLA2, PLC, and extracellular calcium, whereas fMLP-induced ERK phosphorylation does not involve the PKC-γ isoform and extracellular calcium. PAF-induced p38 phosphorylation involves PLA2, whereas fMLP-induced p38 activation is PLC dependent.

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  1. Department of Surgery, Kaohsiung Veterans General Hospital, National Yang-Ming Medical University, Taipei

    Lee-Wei Chen

  2. Department of Biological Sciences, National Sun Yat-Sen University, 70 Lien-Hai Road, Kaohsiung, Taiwan

    Min-Wai Lin & Ching-Mei Hsu

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Chen, LW., Lin, MW. & Hsu, CM. Different pathways leading to activation of extracellular signal-regulated kinase and p38 MAP kinase by formyl-methionyl-leucyl-phenylalanine or platelet activating factor in human neutrophils. J Biomed Sci 12, 311–319 (2005). https://doi.org/10.1007/s11373-005-1704-1

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