| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
2 Integrin Activation Involves Src Kinases and a Redox-Regulated Activation of p38 MAPK1
Institut National de la Santé et de la Recherche Médicale U507, Necker Hospital, Paris, France
We previously demonstrated that the TNF-
-induced inside-out signaling leading to 
2 integrin activation is redox regulated. To identify kinases involved in this pathway, the effects of kinase inhibitors on the expression of 2 integrin activation neoepitope (clone 24) were investigated. We show that both p38 MAPK (inhibited by SB203580) and Src kinases (inhibited by PP2) are involved in 2 integrin activation by TNF and oxidants in human neutrophils. Src kinases appeared constitutively active in resting neutrophils and not further activated by TNF or oxidants in nonadherent conditions. However, PP2 blocked both TNF-induced expression of the 24 epitope and cell adhesion promoted by the integrin activating anti-CD18 KIM185 mAb, showing that both the inside-out and the outside-in signaling involve Src kinases. p38 MAPK was activated by TNF and oxidants in nonadherent conditions i.e., with 10 mM EDTA. This activation in EDTA resulted in CD11b, CD35 and CD66 up-regulation and in an oxidative response, all blocked by SB203580 and PP2. p38 MAPK was not activated upon direct integrin activation by KIM185 mAb. Thus, p38 activation allows the study to distinguish the initial transduction pathway leading to 2 integrin activation from the signaling resulting from integrin engagement. Finally, p38 MAPK activation by TNF was blocked by diphenylene iodonium, an inhibitor of flavoprotein oxidoreductase, and by the free radical scavenger N-acetylcystein. Taken together, these results demonstrate, for the first time, that constitutively activated Src tyrosine kinases and a redox-regulated activation of p38 MAPK are involved in TNF inside-out signaling leading to 2 integrin activation.
This article has been cited by other articles:
|
|
 |
|
  S. J. Mathew, D. Haubert, M. Kronke, and M. Leptin Looking beyond death: a morphogenetic role for the TNF signalling pathway J. Cell Sci., June 15, 2009; 122(12): 1939 - 1946. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Fujita-Yoshigaki, M. Matsuki-Fukushima, and H. Sugiya Inhibition of Src and p38 MAP kinases suppresses the change of claudin expression induced on dedifferentiation of primary cultured parotid acinar cells Am J Physiol Cell Physiol, March 1, 2008; 294(3): C774 - C785. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. G. Moreland, A. P. Davis, J. J. Matsuda, J. S. Hook, G. Bailey, W. M. Nauseef, and F. S. Lamb Endotoxin Priming of Neutrophils Requires NADPH Oxidase-generated Oxidants and Is Regulated by the Anion Transporter ClC-3 J. Biol. Chem., November 23, 2007; 282(47): 33958 - 33967. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. S. Lee, C. Moon, H. W. Lee, E.-M. Park, M.-S. Cho, and J. L. Kang Src Tyrosine Kinases Mediate Activations of NF-{kappa}B and Integrin Signal during Lipopolysaccharide-Induced Acute Lung Injury J. Immunol., November 15, 2007; 179(10): 7001 - 7011. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Brachemi, A. Mambole, F. Fakhouri, L. Mouthon, L. Guillevin, P. Lesavre, and L. Halbwachs-Mecarelli Increased Membrane Expression of Proteinase 3 during Neutrophil Adhesion in the Presence of Anti Proteinase 3 Antibodies J. Am. Soc. Nephrol., August 1, 2007; 18(8): 2330 - 2339. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-L. Lee, M.-J. Wang, P.-R. Sudhir, G.-D. Chen, C.-W. Chi, and J.-Y. Chen Osteopontin Promotes Integrin Activation through Outside-In and Inside-Out Mechanisms: OPN-CD44V Interaction Enhances Survival in Gastrointestinal Cancer Cells Cancer Res., March 1, 2007; 67(5): 2089 - 2097. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Polenghi, F. Bossi, F. Fischetti, P. Durigutto, A. Cabrelle, N. Tamassia, M. A. Cassatella, C. Montecucco, F. Tedesco, and M. de Bernard The Neutrophil-Activating Protein of Helicobacter pylori Crosses Endothelia to Promote Neutrophil Adhesion In Vivo J. Immunol., February 1, 2007; 178(3): 1312 - 1320. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. E. Kilpatrick, S. Sun, D. Mackie, F. Baik, H. Li, and H. M. Korchak Regulation of TNF mediated antiapoptotic signaling in human neutrophils: role of {delta}-PKC and ERK1/2 J. Leukoc. Biol., December 1, 2006; 80(6): 1512 - 1521. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Lokuta and A. Huttenlocher TNF-{alpha} promotes a stop signal that inhibits neutrophil polarization and migration via a p38 MAPK pathway J. Leukoc. Biol., July 1, 2005; 78(1): 210 - 219. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Zhao and G. M. Bokoch Critical Role of Proline-Rich Tyrosine Kinase 2 in Reversion of the Adhesion-Mediated Suppression of Reactive Oxygen Species Generation by Human Neutrophils J. Immunol., June 15, 2005; 174(12): 8049 - 8055. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Strassheim, J.-Y. Kim, J.-S. Park, S. Mitra, and E. Abraham Involvement of SHIP in TLR2-Induced Neutrophil Activation and Acute Lung Injury J. Immunol., June 15, 2005; 174(12): 8064 - 8071. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Sendide, N. E. Reiner, J. S. I. Lee, S. Bourgoin, A. Talal, and Z. Hmama Cross-Talk between CD14 and Complement Receptor 3 Promotes Phagocytosis of Mycobacteria: Regulation by Phosphatidylinositol 3-Kinase and Cytohesin-1 J. Immunol., April 1, 2005; 174(7): 4210 - 4219. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
