Activation of extracellular signal-regulated kinase couples platelet-activating factor-induced adhesion and delayed apoptosis of human neutrophils
| Autor: | John S.D. Chan, Tarek Khreiss, János G. Filep, Levente Jozsef |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
MAPK/ERK pathway
Time Factors Cell Survival Neutrophils Apoptosis Mitogen-activated protein kinase kinase MAP2K7 Wortmannin Phosphatidylinositol 3-Kinases chemistry.chemical_compound Cell Adhesion Humans ASK1 Enzyme Inhibitors Phosphorylation Platelet Activating Factor Extracellular Signal-Regulated MAP Kinases Protein kinase B Flavonoids Inflammation CD11b Antigen Dose-Response Relationship Drug MAP kinase kinase kinase Caspase 3 Akt/PKB signaling pathway Cell Biology Flow Cytometry Up-Regulation Cell biology Androstadienes Enzyme Activation chemistry CD18 Antigens Caspases bcl-Associated Death Protein Carrier Proteins Granulocytes Signal Transduction |
| Zdroj: | Cellular Signalling. 16:801-810 |
| ISSN: | 0898-6568 |
| DOI: | 10.1016/j.cellsig.2003.12.005 |
| Popis: | Platelet-activating factor (PAF) promotes adhesion of neutrophil granulocytes to the endothelium, which is also linked to neutrophil survival. Here we report that PAF can prolong neutrophil survival by suppressing spontaneous apoptosis. PAF induced concurrent activation of the Ras/Raf-1/mitogen-activated protein kinase kinase (MAPKK)/extracellular signal-regulated kinase (ERK) and phosphatidylinositol 3-kinase/Akt pathways. ERK activation tightly correlated with up-regulation of CD11b/CD18 expression and β2-integrin-dependent homotypic adhesion. These actions of PAF were markedly attenuated by the MAPKK/ERK inhibitor PD98059, but not by the phosphatidylinositol 3-kinase inhibitor wortmannin. By contrast, concurrent activation of ERK and Akt was required to inhibit caspase-3 activation and consequently to delay apoptosis. Consistently, pharmacological inhibition of either ERK or Akt partially reversed the anti-apoptotic action of PAF; however, they did not produce additive inhibition. These results indicate that PAF-induced activation of ERK contributes to both the expression of the pro-adhesive phenotype and repression of neutrophil apoptosis, thereby amplifying the inflammatory response. |
| Databáze: | OpenAIRE |
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