This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Godambe, S. A.
Right arrow Articles by English, B. K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Godambe, S. A.
Right arrow Articles by English, B. K.

 Previous Article  |  Next Article 

Clinical and Diagnostic Laboratory Immunology, May 2004, p. 525-531, Vol. 11, No. 3
1071-412X/04/$08.00+0     DOI: 10.1128/CDLI.11.3.525-531.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Role of vav1 in the Lipopolysaccharide-Mediated Upregulation of Inducible Nitric Oxide Synthase Production and Nuclear Factor for Interleukin-6 Expression Activity in Murine Macrophages

Sandip A. Godambe,1,2 Katherine M. Knapp,1,3,4 Elizabeth A. Meals,1,3 and B. Keith English1,3*

Children's Foundation Research Center at Le Bonheur Children's Medical Center,1 Division of Emergency Medicine,2 Division of Infectious Diseases, Department of Pediatrics, University of Tennessee Health Science Center,3 Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee4

Received 14 May 2003/ Returned for modification 9 December 2003/ Accepted 18 February 2004

vav1 has been shown to play a key role in lymphocyte development and activation, but its potential importance in macrophage activation has received little attention. We have previously reported that exposure of macrophages to bacterial lipopolysaccharide (LPS) leads to increased activity of hck and other src-related tyrosine kinases and to the prompt phosphorylation of vav1 on tyrosine. In this study, we tested the role of vav1 in macrophage responses to LPS, focusing on the upregulation of nuclear factor for interleukin-6 expression (NF-IL-6) activity and inducible nitric oxide synthase (iNOS) protein accumulation in RAW-TT10 murine macrophages. We established a series of stable cell lines expressing three mutant forms of vav1 in a tetracycline-regulatable fashion: (i) a form producing a truncated protein, vavC; (ii) a form containing a point mutation in the regulatory tyrosine residue, vavYF174; and (iii) a form with an in-frame deletion of 6 amino acids required for the guanidine nucleotide exchange factor (GEF) activity of vav1 for rac family GTPases, vavGEFmt. Expression of the truncated mutant (but not the other two mutants) has been reported to interfere with T-cell activation. In contrast, we now demonstrate that expression of any of the three mutant forms of vav1 in RAW-TT10 cells consistently inhibited LPS-mediated increases in iNOS protein accumulation and NF-IL-6 activity. These data provide direct evidence for a role for vav1 in LPS-mediated macrophage activation and iNOS production and suggest that vav1 functions in part via activation of NF-IL-6. Furthermore, these findings indicate that the GEF activity of vav1 is required for its ability to mediate macrophage activation by LPS.

* Corresponding author. Mailing address: Department of Pediatrics, Children's Foundation Research Center, Le Bonheur Children's Medical Center, 50 N. Dunlap, Memphis, TN 38103. Phone: (901) 572-5376. Fax: (901) 572-5036. E-mail: kenglish{at}utmem.edu.

Clinical and Diagnostic Laboratory Immunology, May 2004, p. 525-531, Vol. 11, No. 3
1071-412X/04/$08.00+0     DOI: 10.1128/CDLI.11.3.525-531.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.





Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»