| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
,
,
Departments of
*
Physiology and Biophysics and
Medicine, Wright State University, Dayton, OH 45435; and
Research Service, Department of Veterans Affairs, Department of Medicine, Wright State University, Dayton, OH 45428
GM-CSF stimulates proliferation of myeloid precursors in bone marrow and primes mature leukocytes for enhanced functionality. We demonstrate that GM-CSF is a powerful chemotactic and chemokinetic agent for human neutrophils. GM-CSF-induced chemotaxis is time dependent and is specifically neutralized with Abs directed to either the ligand itself or its receptor. Maximal chemotactic response was achieved at 
7 nM GM-CSF, and the EC50 was 0.9 nM. Both concentrations are similar to the effective concentrations of IL-8 and less than the effective concentrations of other neutrophil chemoattractants such as neutrophil-activating peptide-78, granulocyte chemotactic protein-2, leukotriene B4, and FMLP. GM-CSF also acts as a chemoattractant for native cells bearing the GM-CSF receptor, such as monocytes, as well as for GM-CSF receptor-bearing myeloid cell lines, HL60 (promyelomonocyte leukemic cell line) and MPD (myeloproliferative disorder cell line), following differentiation induction. GM-CSF induced a rapid, transient increase in F-actin polymerization and the formation of focal contact rings in neutrophils, which are prerequisites for cell migration. The mechanism of GM-CSF-induced chemotaxis appears to involve the cell signaling molecule, ribosomal p70 S6 kinase (p70S6K). Both p70S6K enzymatic activity and T421/S424 and T389 phosphorylation are markedly increased with GM-CSF. In addition, the p70S6K inhibitor hamartin transduced into cells as active protein, interfered with GM-CSF-dependent migration, and attenuated p70S6K phosphorylation. These data indicate that GM-CSF exhibits chemotactic functionality and suggest new avenues for the investigation of the molecular basis of chemotaxis as it relates to inflammation and tissue injury.
This article has been cited by other articles:
|
|
 |
|
  F. Arcuri, P. Toti, L. Buchwalder, A. Casciaro, M. Cintorino, F. Schatz, B. Rybalov, and C. J. Lockwood Mechanisms of Leukocyte Accumulation and Activation in Chorioamnionitis: Interleukin 1{beta} and Tumor Necrosis Factor {alpha} Enhance Colony Stimulating Factor 2 Expression in Term Decidua Reproductive Sciences, May 1, 2009; 16(5): 453 - 461. [Abstract] [PDF]
|
|
|
|
 |
|
 T Weichhart and M D Saemann The PI3K/Akt/mTOR pathway in innate immune cells: emerging therapeutic applications Ann Rheum Dis, December 1, 2008; 67(Suppl_3): iii70 - iii74. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. S. Marino, B. J. Tausch, C. L. Dearth, M. V. Manacci, T. J. McLoughlin, S. J. Rakyta, M. P. Linsenmayer, and F. X. Pizza {beta}2-Integrins contribute to skeletal muscle hypertrophy in mice Am J Physiol Cell Physiol, October 1, 2008; 295(4): C1026 - C1036. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Tirouvanziam, Y. Gernez, C. K. Conrad, R. B. Moss, I. Schrijver, C. E. Dunn, Z. A. Davies, L. A. Herzenberg, and L. A. Herzenberg Profound functional and signaling changes in viable inflammatory neutrophils homing to cystic fibrosis airways PNAS, March 18, 2008; 105(11): 4335 - 4339. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. M. Lehmann, A. M. P. B. Seneviratne, and A. V. Smrcka Small Molecule Disruption of G Protein {beta}{gamma} Subunit Signaling Inhibits Neutrophil Chemotaxis and Inflammation Mol. Pharmacol., February 1, 2008; 73(2): 410 - 418. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Choi, B. Salanova, S. Rolle, M. Wellner, W. Schneider, F. C. Luft, and R. Kettritz Short-Term Heat Exposure Inhibits Inflammation by Abrogating Recruitment of and Nuclear Factor-{kappa}B Activation in Neutrophils Exposed to Chemotactic Cytokines Am. J. Pathol., February 1, 2008; 172(2): 367 - 777. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Gomez-Cambronero, M. Di Fulvio, and K. Knapek Understanding phospholipase D (PLD) using leukocytes: PLD involvement in cell adhesion and chemotaxis J. Leukoc. Biol., August 1, 2007; 82(2): 272 - 281. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Segarra, L. Balenci, T. Drenth, F. Maina, and F. Lamballe Combined Signaling through ERK, PI3K/AKT, and RAC1/p38 Is Required for Met-triggered Cortical Neuron Migration J. Biol. Chem., February 24, 2006; 281(8): 4771 - 4778. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. D. Kobayashi, J. M. Voyich, A. R. Whitney, and F. R. DeLeo Spontaneous neutrophil apoptosis and regulation of cell survival by granulocyte macrophage-colony stimulating factor J. Leukoc. Biol., December 1, 2005; 78(6): 1408 - 1418. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Di Fulvio and J. Gomez-Cambronero Phospholipase D (PLD) gene expression in human neutrophils and HL-60 differentiation J. Leukoc. Biol., June 1, 2005; 77(6): 999 - 1007. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.V. Fahey, T.M Schaefer, J.Y. Channon, and C.R. Wira Secretion of cytokines and chemokines by polarized human epithelial cells from the female reproductive tract Hum. Reprod., June 1, 2005; 20(6): 1439 - 1446. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Schaerli, M. Britschgi, M. Keller, U. C. Steiner, L. S. Steinmann, B. Moser, and W. J. Pichler Characterization of Human T Cells That Regulate Neutrophilic Skin Inflammation J. Immunol., August 1, 2004; 173(3): 2151 - 2158. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
