Actin reorganization and morphological changes in human neutrophils stimulated by TNF, GM-CSF, and G-CSF: the role of MAP kinases
| Autor: | Noriko Kamata, Seiichi Kitagawa, Kenichi Suzuki, Masamitsu Ishii, Kensaku Mizuno, Takayuki Kato, Hiromi Kobayashi, Fumihiko Hato, Haruo Kutsuna |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Adult
Neutrophils Polymers Pyridines Physiology medicine.medical_treatment Stimulation macromolecular substances Granulocyte Biology p38 Mitogen-Activated Protein Kinases Granulocyte Colony-Stimulating Factor medicine Humans Enzyme Inhibitors Phosphorylation Flavonoids Tumor Necrosis Factor-alpha Kinase Microfilament Proteins Imidazoles Granulocyte-Macrophage Colony-Stimulating Factor Cell Biology Actins Recombinant Proteins Cell biology Enzyme Activation N-Formylmethionine Leucyl-Phenylalanine Granulocyte macrophage colony-stimulating factor medicine.anatomical_structure Cytokine Actin Depolymerizing Factors Mitogen-activated protein kinase biology.protein Tumor necrosis factor alpha Mitogen-Activated Protein Kinases Signal transduction medicine.drug |
| Zdroj: | American Journal of Physiology-Cell Physiology. 286:C55-C64 |
| ISSN: | 1522-1563 0363-6143 |
| Popis: | Stimulation of human neutrophils with tumor necrosis factor-α (TNF), granulocyte-macrophage colony-stimulating factor (GM-CSF), or granulocyte CSF (G-CSF) resulted in decreased fluorescence intensity of FITC-phalloidin (actin depolymerization) and morphological changes. Cytokine-induced actin depolymerization was dependent on the concentration of cytokines used as stimuli. The maximal changes were detected at 10 min after stimulation with TNF or GM-CSF and at 20 min after stimulation with G-CSF. Cytokine-induced actin depolymerization was sustained for at least 30 min after stimulation. In contrast, N-formyl-methionyl-leucyl-phenylalanine (FMLP) rapidly (within 45 s) induced an increase in the fluorescence intensity of FITC-phalloidin (actin polymerization) and morphological changes. TNF- and GM-CSF-induced actin depolymerization and morphological changes, but not FMLP-induced responses, were partially inhibited by either PD-98059, an inhibitor of mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) kinase, or SB-203580, an inhibitor of p38 MAPK, and were almost completely abolished by these inhibitors in combination. G-CSF-induced responses were almost completely abolished by PD-98059 and were unaffected by SB-203580. These findings are consistent with the ability of these cytokines to activate the distinct MAPK subtype cascade in human neutrophils. Phosphorylated ERK and p38 MAPK were not colocalized with F-actin in neutrophils stimulated by cytokines or FMLP. Furthermore, FMLP-induced polarization and actin polymerization were prevented by cytokine pretreatment. These findings suggest that TNF, GM-CSF, and G-CSF induce actin depolymerization and morphological changes through activation of ERK and/or p38 MAPK and that cytokine-induced actin reorganization may be partly responsible for the inhibitory effect of these cytokines on neutrophil chemotaxis. |
| Databáze: | OpenAIRE |
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