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or FMLP Stimulation1
Departments of
*
Physiology,
Pathology, and
Medicine, University of Connecticut Health Center, Farmington, CT 06030; and
§
Institute for Neuroscience, Northwestern University, Chicago, IL 60611
Mitogen-activated protein (MAP) kinase-mediated signal-transduction
pathways convert extracellular stimulation into a variety of cellular
functions. However, the roles of MAP kinases in neutrophils are not
well understood yet. Protein phosphorylation analysis of cellular MAP
kinases indicates that exposure of human neutrophils to chemotactic
factor FMLP as well as granulocyte-macrophage CSF, PMA, or ionomycin
rapidly induced the activation of p38 and p44/42 MAP kinases, but
stimulation with inflammatory cytokine TNF-
triggered the activation
of p38 MAP kinase only. To study the cellular functions of these MAP
kinases, the inhibitor SB20358, which specifically inhibited enzymatic
activity of cellular p38 MAP kinase, and the inhibitor PD98059, which
specifically blocked the induced protein phosphorylation and activation
of p44/42 MAP kinase in intact neutrophils, were utilized. Inhibition
of the cellular p38 MAP kinase activation almost completely abolished
the TNF--stimulated IL-8 production and superoxide generation of
human neutrophils. In addition, the FMLP-induced neutrophil chemotaxis
as well as superoxide generation were suppressed markedly by inhibiting
the activation of cellular p38 MAP kinase, but not p44/42 MAP kinase.
Moreover, RIA indicates that the activation of cellular p38 MAP kinase
was required for the neutrophil IL-8 production stimulated by
granulocyte-macrophage CSF or LPS as well as TNF-, but not for that
induced by PMA or ionomycin. These results demonstrate that the
activation of cellular p38 MAP kinase is indispensable for the TNF--
or FMLP-mediated cellular functions in human neutrophils, and suggest
that p38 MAP kinase may play a different role in response to distinct
stimulation.
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 Q. Jing, S.-M. Xin, W.-B. Zhang, P. Wang, Y.-W. Qin, and G. Pei Lysophosphatidylcholine Activates p38 and p42/44 Mitogen-Activated Protein Kinases in Monocytic THP-1 Cells, but Only p38 Activation Is Involved in Its Stimulated Chemotaxis Circ. Res., July 7, 2000; 87(1): 52 - 59. [Abstract] [Full Text] [PDF]
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P. Y. Coxon, M. J. Rane, D. W. Powell, J. B. Klein, and K. R. McLeish Differential Mitogen-Activated Protein Kinase Stimulation by Fc{gamma} Receptor IIa and Fc{gamma} Receptor IIIb Determines the Activation Phenotype of Human Neutrophils J. Immunol., June 15, 2000; 164(12): 6530 - 6537. [Abstract] [Full Text] [PDF]
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A. Mocsai, Z. Jakus, T. Vantus, G. Berton, C. A. Lowell, and E. Ligeti Kinase Pathways in Chemoattractant-Induced Degranulation of Neutrophils: The Role of p38 Mitogen-Activated Protein Kinase Activated by Src Family Kinases J. Immunol., April 15, 2000; 164(8): 4321 - 4331. [Abstract] [Full Text] [PDF]
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S. I. Simon, Y. Hu, D. Vestweber, and C. W. Smith Neutrophil Tethering on E-Selectin Activates {beta}2 Integrin Binding to ICAM-1 Through a Mitogen-Activated Protein Kinase Signal Transduction Pathway J. Immunol., April 15, 2000; 164(8): 4348 - 4358. [Abstract] [Full Text] [PDF]
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E. A. Albanyan, J. G. Vallejo, C. W. Smith, and M. S. Edwards Nonopsonic Binding of Type III Group B Streptococci to Human Neutrophils Induces Interleukin-8 Release Mediated by the p38 Mitogen-Activated Protein Kinase Pathway Infect. Immun., April 1, 2000; 68(4): 2053 - 2060. [Abstract] [Full Text] [PDF]
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J. A. Nick, S. K. Young, K. K. Brown, N. J. Avdi, P. G. Arndt, B. T. Suratt, M. S. Janes, P. M. Henson, and G. S. Worthen Role of p38 Mitogen-Activated Protein Kinase in a Murine Model of Pulmonary Inflammation J. Immunol., February 15, 2000; 164(4): 2151 - 2159. [Abstract] [Full Text] [PDF]
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 D. A. Partrick, E. E. Moore, P. J. Offner, D. R. Meldrum, D. Y. Tamura, J. L. Johnson, and C. C. Silliman Maximal Human Neutrophil Priming for Superoxide Production and Elastase Release Requires p38 Mitogen-Activated Protein Kinase Activation Arch Surg, February 1, 2000; 135(2): 219 - 225. [Abstract] [Full Text] [PDF]
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N. Perskvist, L. Zheng, and O. Stendahl Activation of Human Neutrophils by Mycobacterium tuberculosis H37Ra Involves Phospholipase C{gamma}2, Shc Adapter Protein, and p38 Mitogen-Activated Protein Kinase J. Immunol., January 15, 2000; 164(2): 959 - 965. [Abstract] [Full Text] [PDF]
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 I. Daniels, J. Fletcher, and A. P. Haynes Role of p38 in the Priming of Human Neutrophils by Peritoneal Dialysis Effluent Clin. Vaccine Immunol., November 1, 1999; 6(6): 878 - 884. [Abstract] [Full Text] [PDF]
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S. A. Wadsworth, D. E. Cavender, S. A. Beers, P. Lalan, P. H. Schafer, E. A. Malloy, W. Wu, B. Fahmy, G. C. Olini, J. E. Davis, et al. RWJ 67657, a Potent, Orally Active Inhibitor of p38 Mitogen-Activated Protein Kinase J. Pharmacol. Exp. Ther., November 1, 1999; 291(2): 680 - 687. [Abstract] [Full Text]
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J. P. Lian, R. Huang, D. Robinson, and J. A. Badwey Activation of p90RSK and cAMP Response Element Binding Protein in Stimulated Neutrophils: Novel Effects of the Pyridinyl Imidazole SB 203580 on Activation of the Extracellular Signal-Regulated Kinase Cascade J. Immunol., October 15, 1999; 163(8): 4527 - 4536. [Abstract] [Full Text] [PDF]
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J. L. Johnson, E. E. Moore, D. A. Patrick, D. Y. Tamura, G. Zallen, D. J. Elzi, and C. C. Silliman Extracellular Signal-Related Kinase 1/2 and p38 Mitogen-Activated Protein Kinase Pathways Serve Opposite Roles in Neutrophil Cytotoxicity Arch Surg, October 1, 1999; 134(10): 1074 - 1078. [Abstract] [Full Text] [PDF]
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N. Geijsen, S. van Delft, J. A.M. Raaijmakers, J.-W. J. Lammers, J. G. Collard, L. Koenderman, and P. J. Coffer Regulation of p21rac Activation in Human Neutrophils Blood, August 1, 1999; 94(3): 1121 - 1130. [Abstract] [Full Text] [PDF]
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S. B. Rizoli, O. D. Rotstein, and A. Kapus Cell Volume-dependent Regulation of L-selectin Shedding in Neutrophils. A ROLE FOR p38 MITOGEN-ACTIVATED PROTEIN KINASE J. Biol. Chem., July 30, 1999; 274(31): 22072 - 22080. [Abstract] [Full Text] [PDF]
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R. M. Heuertz, S. M. Tricomi, U. R. Ezekiel, and R. O. Webster C-reactive Protein Inhibits Chemotactic Peptide-induced p38 Mitogen-activated Protein Kinase Activity and Human Neutrophil Movement J. Biol. Chem., June 18, 1999; 274(25): 17968 - 17974. [Abstract] [Full Text] [PDF]
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S. Arbabi, I. Garcia, G. J. Bauer, and R. V. Maier Alcohol (Ethanol) Inhibits IL-8 and TNF: Role of the p38 Pathway J. Immunol., June 15, 1999; 162(12): 7441 - 7445. [Abstract] [Full Text] [PDF]
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I. Feoktistov, A. E. Goldstein, and I. Biaggioni Role of p38 Mitogen-Activated Protein Kinase and Extracellular Signal-Regulated Protein Kinase Kinase in Adenosine A2B Receptor-Mediated Interleukin-8 Production in Human Mast Cells Mol. Pharmacol., April 1, 1999; 55(4): 726 - 734. [Abstract] [Full Text]
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K. K. Hale, D. Trollinger, M. Rihanek, and C. L. Manthey Differential Expression and Activation of p38 Mitogen-Activated Protein Kinase {alpha}, {beta}, {gamma}, and {delta} in Inflammatory Cell Lineages J. Immunol., April 1, 1999; 162(7): 4246 - 4252. [Abstract] [Full Text] [PDF]
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D. D. Browning, N. D. Windes, and R. D. Ye Activation of p38 Mitogen-activated Protein Kinase by Lipopolysaccharide in Human Neutrophils Requires Nitric Oxide-dependent cGMP Accumulation J. Biol. Chem., January 1, 1999; 274(1): 537 - 542. [Abstract] [Full Text] [PDF]
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 R. Huang, J. P. Lian, D. Robinson, and J. A. Badwey Neutrophils Stimulated with a Variety of Chemoattractants Exhibit Rapid Activation of p21-Activated Kinases (Paks): Separate Signals Are Required for Activation and Inactivation of Paks Mol. Cell. Biol., December 1, 1998; 18(12): 7130 - 7138. [Abstract] [Full Text]
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 J. Chen, Y. Sun, and G. J. Nabel Regulation of the Proinflammatory Effects of Fas Ligand (CD95L) Science, November 27, 1998; 282(5394): 1714 - 1717. [Abstract] [Full Text]
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J. P. Lian, R. Huang, D. Robinson, and J. A. Badwey Products of Sphingolipid Catabolism Block Activation of the p21-Activated Protein Kinases in Neutrophils J. Immunol., October 15, 1998; 161(8): 4375 - 4381. [Abstract] [Full Text] [PDF]
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P. A. Detmers, D. Zhou, E. Polizzi, R. Thieringer, W. A. Hanlon, S. Vaidya, and V. Bansal Role of Stress-Activated Mitogen-Activated Protein Kinase (p38) in {beta}2-Integrin-Dependent Neutrophil Adhesion and the Adhesion-Dependent Oxidative Burst J. Immunol., August 15, 1998; 161(4): 1921 - 1929. [Abstract] [Full Text] [PDF]
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R. A. Ward, M. Nakamura, and K. R. McLeish Priming of the Neutrophil Respiratory Burst Involves p38 Mitogen-activated Protein Kinase-dependent Exocytosis of Flavocytochrome b558-containing Granules J. Biol. Chem., November 17, 2000; 275(47): 36713 - 36719. [Abstract] [Full Text] [PDF]
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S. Bechoua and L. W. Daniel Phospholipase D Is Required in the Signaling Pathway Leading to p38 MAPK Activation in Neutrophil-like HL-60 Cells, Stimulated by N-Formyl-methionyl-leucyl-phenylalanine J. Biol. Chem., August 17, 2001; 276(34): 31752 - 31759. [Abstract] [Full Text] [PDF]
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J. E. Smolen, T. K. Petersen, C. Koch, S. J. O'Keefe, W. A. Hanlon, S. Seo, D. Pearson, M. C. Fossett, and S. I. Simon L-Selectin Signaling of Neutrophil Adhesion and Degranulation Involves p38 Mitogen-activated Protein Kinase J. Biol. Chem., May 19, 2000; 275(21): 15876 - 15884. [Abstract] [Full Text] [PDF]
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 O. Werz, J. Klemm, B. Samuelsson, and O. Radmark 5-Lipoxygenase is phosphorylated by p38 kinase-dependent MAPKAP kinases PNAS, May 9, 2000; 97(10): 5261 - 5266. [Abstract] [Full Text] [PDF]
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