|
|
Blood, 1 May 2007, Vol. 109, No. 9, pp. 4028-4037.
Prepublished online as a Blood First Edition Paper on January 3, 2007; DOI 10.1182/blood-2006-10-055319.
 Previous Article | Next Article 
Submitted October 30, 2006
Accepted December 22, 2006
Tumor suppressor PTEN is a physiological suppressor of chemoattractant-mediated neutrophil functions
Kulandayan K Subramanian, Yonghui Jia, Daocheng Zhu, Benjamin T Simms, Hakryul Jo, Hidenori Hattori, Jian You, Joseph P Mizgerd, and Hongbo R Luo*
Dept of Pathology, Harvard Medical School, Dept of Lab Medicine and Joint Prog in Transfusion Medicine; Children's Hospital Boston, Boston, MA, United States
Molecular and Integrative Physiological Sciences Program, Dept of Environmental Health, Harvard School of Public Health, Boston, MA, United States
* Corresponding author; email: hongbo.luo{at}childrens.harvard.edu.
The recruitment and activation of neutrophils at infected tissues is essential for host defense against invading microorganisms. However, excessive neutrophil recruitment or activation can also damage the surrounding tissues and cause unwanted inflammation. Hence, the responsiveness of neutrophils needs to be tightly regulated. In this study, we have investigated the functional role of tumor suppressor PTEN in neutrophils by using a mouse line in which PTEN is disrupted only in myeloid-derived cells. Chemoattractant stimulated PTEN-/- neutrophils displayed significantly higher Akt phosphorylation and actin polymerization. A larger fraction of these neutrophils displayed membrane ruffles in response to chemoattractant stimulation. In addition, chemoattractant-induced transwell migration and superoxide production were also augmented. Single-cell chemotaxis assays showed that PTEN-/- neutrophils have a small (yet statistically significant) defect in directionality. However, these neutrophils also showed an increase in cell speed. As a result, overall chemotaxis, which depends on speed and directionality, was not affected. Consistent with the increased responsiveness of PTEN-/- neutrophils, the in vivo recruitment of these cells to the inflamed peritoneal cavity was significantly enhanced. Thus, as a physiological negative regulator, PTEN should be a promising therapeutic target for modulating neutrophil functions in various infectious and inflammatory diseases.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
Related Article in Blood Online:
-
Braking neutrophils with PTEN
- Lee-Ann H. Allen
Blood 2007 109: 3620-3621.
[Full Text]
[PDF]
This article has been cited by other articles:
|
|
|
|
 
A. Kasorn, P. Alcaide, Y. Jia, K. K. Subramanian, B. Sarraj, Y. Li, F. Loison, H. Hattori, L. E. Silberstein, W. F. Luscinskas, et al.
Focal Adhesion Kinase Regulates Pathogen-Killing Capability and Life Span of Neutrophils via Mediating Both Adhesion-Dependent and -Independent Cellular Signals
J. Immunol.,
July 15, 2009;
183(2):
1032 - 1043.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Sarraj, S. Massberg, Y. Li, A. Kasorn, K. Subramanian, F. Loison, L. E. Silberstein, U. von Andrian, and H. R. Luo
Myeloid-Specific Deletion of Tumor Suppressor PTEN Augments Neutrophil Transendothelial Migration during Inflammation
J. Immunol.,
June 1, 2009;
182(11):
7190 - 7200.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Li, Y. Jia, M. Pichavant, F. Loison, B. Sarraj, A. Kasorn, J. You, B. E. Robson, D. T. Umetsu, J. P. Mizgerd, et al.
Targeted deletion of tumor suppressor PTEN augments neutrophil function and enhances host defense in neutropenia-associated pneumonia
Blood,
May 14, 2009;
113(20):
4930 - 4941.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Shi, J. Zhang, M. Mullin, B. Dong, A. S. Alberts, and K. A. Siminovitch
The mDial Formin Is Required for Neutrophil Polarization, Migration, and Activation of the LARG/RhoA/ROCK Signaling Axis during Chemotaxis
J. Immunol.,
March 15, 2009;
182(6):
3837 - 3845.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Jo, Y. Jia, K. K. Subramanian, H. Hattori, and H. R. Luo
Cancer Cell-Derived Clusterin Modulates the Phosphatidylinositol 3'-Kinase-Akt Pathway through Attenuation of Insulin-Like Growth Factor 1 during Serum Deprivation
Mol. Cell. Biol.,
July 1, 2008;
28(13):
4285 - 4299.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. Kolsch, P. G. Charest, and R. A. Firtel
The regulation of cell motility and chemotaxis by phospholipid signaling
J. Cell Sci.,
March 1, 2008;
121(5):
551 - 559.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. J. Harris, R. V. Parry, J. Westwick, and S. G. Ward
Phosphoinositide Lipid Phosphatases: Natural Regulators of Phosphoinositide 3-Kinase Signaling in T Lymphocytes
J. Biol. Chem.,
February 1, 2008;
283(5):
2465 - 2469.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Herzmark, K. Campbell, F. Wang, K. Wong, H. El-Samad, A. Groisman, and H. R. Bourne
Bound attractant at the leading vs. the trailing edge determines chemotactic prowess
PNAS,
August 14, 2007;
104(33):
13349 - 13354.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Wessels, D. F. Lusche, S. Kuhl, P. Heid, and D. R. Soll
PTEN plays a role in the suppression of lateral pseudopod formation during Dictyostelium motility and chemotaxis
J. Cell Sci.,
August 1, 2007;
120(15):
2517 - 2531.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Chakrabarti, P. Blair, and J. E. Freedman
CD40-40L Signaling in Vascular Inflammation
J. Biol. Chem.,
June 22, 2007;
282(25):
18307 - 18317.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
