NDLI: Tumor suppressor PTEN is a physiologic suppressor of chemoattractant-mediated neutrophil functions

Content Provider	PubMed Central
Author	Subramanian, Kulandayan K. Jia, Yonghui Zhu, Daocheng Simms, Benjamin T. Jo, Hakryul Hattori, Hidenori You, Jian Mizgerd, Joseph P. Luo, Hongbo R.
Copyright Year	2007
Abstract	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 responsivenessof PTEN −/− neutrophils, the in vivo recruitment of these cells to the inflamed peritoneal cavity was significantly enhanced. Thus, as a physiologic-negative regulator, PTEN should be a promising therapeutic target for modulating neutrophil functions in various infectious and inflammatory diseases.
Related Links	http://dx.doi.org/10.1182/blood-2006-10-055319
Ending Page	4037
Page Count	10
Starting Page	4028
File Format	PDF
ISSN	00064971
e-ISSN	15280020
Journal	Blood
Issue Number	9
Volume Number	109
Language	English
Publisher	American Society of Hematology
Publisher Date	2007-05-01
Access Restriction	Open
Rights Holder	American Society of Hematology
Subject Keyword	Immunology Cell Biology Biochemistry Hematology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Cell Biology Hematology Biochemistry Immunology

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