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 HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Shi, Z.-Z.
Right arrow Articles by Lieberman, M. W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Shi, Z.-Z.
Right arrow Articles by Lieberman, M. W.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, August 2001, p. 5389-5395, Vol. 21, No. 16
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.16.5389-5395.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Disruption of gamma -Glutamyl Leukotrienase Results in Disruption of Leukotriene D4 Synthesis In Vivo and Attenuation of the Acute Inflammatory Response

Zheng-Zheng Shi,1 Bing Han,1 Geetha M. Habib,1 Martin M. Matzuk,1,2,3 and Michael W. Lieberman1,2,*

Departments of Pathology,1 Molecular and Cellular Biology,2 and Molecular and Human Genetics,3 Baylor College of Medicine, Houston, Texas 77030

Received 3 April 2001/Accepted 23 May 2001

To study the function of gamma -glutamyl leukotrienase (GGL), a newly identified member of the gamma -glutamyl transpeptidase (GGT) family, we generated null mutations in GGL (GGLtm1) and in both GGL and GGT (GGLtm1-GGTtm1) by a serial targeting strategy using embryonic stem cells. Mice homozygous for GGLtm1 show no obvious phenotypic changes. Mice deficient in both GGT and GGL have a phenotype similar to the GGT-deficient mice, but ~70% of these mice die before 4 weeks of age, at least 2 months earlier than mice deficient only in GGT. These double-mutant mice are unable to cleave leukotriene C4 (LTC4) to LTD4, indicating that this conversion is completely dependent on the two enzymes, and in some organs (spleen and uterus) deletion of GGL alone abolished more than 90% of this activity. In an experimental model of peritonitis, GGL alone is responsible for the generation of peritoneal LTD4. Further, during the development of peritonitis, GGL-deficient mice show an attenuation in neutrophil recruitment but not of plasma protein influx. These findings demonstrate an important role for GGL in the inflammatory response and suggest that LTC4 and LTD4 have distinctly different functions in the inflammatory process.

* Corresponding author. Mailing address: Department of Pathology, One Baylor Plaza, Baylor College of Medicine, Houston, TX 77030. Phone: (713) 798-6501. Fax: (713) 798-6001. E-mail: mikel{at}bcm.tmc.edu.

Molecular and Cellular Biology, August 2001, p. 5389-5395, Vol. 21, No. 16
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.16.5389-5395.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Buczynski, M. W., Dumlao, D. S., Dennis, E. A. (2009). Thematic Review Series: Proteomics. An integrated omics analysis of eicosanoid biology. J. Lipid Res. 50: 1015-1038 [Abstract] [Full Text]  
  • Martin, M. N., Saladores, P. H., Lambert, E., Hudson, A. O., Leustek, T. (2007). Localization of Members of the {gamma}-Glutamyl Transpeptidase Family Identifies Sites of Glutathione and Glutathione S-Conjugate Hydrolysis. Plant Physiol. 144: 1715-1732 [Abstract] [Full Text]  
  • Murai, A., Abe, M., Hayashi, Y., Sakata, N., Katsuragi, T., Tanaka, K. (2005). Comparison Study between the Mechanisms of Allergic Asthma Amelioration by a Cysteinyl-Leukotriene Type 1 Receptor Antagonist Montelukast and Methylprednisolone. J. Pharmacol. Exp. Ther. 312: 432-440 [Abstract] [Full Text]  
  • Peters-Golden, M., Canetti, C., Mancuso, P., Coffey, M. J. (2005). Leukotrienes: Underappreciated Mediators of Innate Immune Responses. J. Immunol. 174: 589-594 [Abstract] [Full Text]  
  • Beller, T. C., Maekawa, A., Friend, D. S., Austen, K. F., Kanaoka, Y. (2004). Targeted Gene Disruption Reveals the Role of the Cysteinyl Leukotriene 2 Receptor in Increased Vascular Permeability and in Bleomycin-induced Pulmonary Fibrosis in Mice. J. Biol. Chem. 279: 46129-46134 [Abstract] [Full Text]  
  • Kanaoka, Y., Boyce, J. A. (2004). Cysteinyl Leukotrienes and Their Receptors: Cellular Distribution and Function in Immune and Inflammatory Responses. J. Immunol. 173: 1503-1510 [Abstract] [Full Text]  
  • Beller, T. C., Friend, D. S., Maekawa, A., Lam, B. K., Austen, K. F., Kanaoka, Y. (2004). Cysteinyl leukotriene 1 receptor controls the severity of chronic pulmonary inflammation and fibrosis. Proc. Natl. Acad. Sci. USA 101: 3047-3052 [Abstract] [Full Text]  
  • Zaitsu, M., Hamasaki, Y., Tsuji, K., Matsuo, M., Fujita, I., Aoki, Y., Ishii, E., Kohashi, O. (2003). Dexamethasone accelerates catabolism of leukotriene C4 in bronchial epithelial cells. Eur Respir J 22: 35-42 [Abstract] [Full Text]  
  • Bandeira-Melo, C., Woods, L. J., Phoofolo, M., Weller, P. F. (2002). Intracrine Cysteinyl Leukotriene Receptor-mediated Signaling of Eosinophil Vesicular Transport-mediated Interleukin-4 Secretion. JEM 196: 841-850 [Abstract] [Full Text]  
  • Han, B., Luo, G., Shi, Z.-Z., Barrios, R., Atwood, D., Liu, W., Habib, G. M., Sifers, R. N., Corry, D. B., Lieberman, M. W. (2002). {gamma}-Glutamyl Leukotrienase, a Novel Endothelial Membrane Protein, Is Specifically Responsible for Leukotriene D4 Formation in Vivo. Am. J. Pathol. 161: 481-490 [Abstract] [Full Text]  
  • Maekawa, A., Austen, K. F., Kanaoka, Y. (2002). Targeted Gene Disruption Reveals the Role of Cysteinyl Leukotriene 1 Receptor in the Enhanced Vascular Permeability of Mice Undergoing Acute Inflammatory Responses. J. Biol. Chem. 277: 20820-20824 [Abstract] [Full Text]  
  • Mellor, E. A., Austen, K. F., Boyce, J. A. (2002). Cysteinyl Leukotrienes and Uridine Diphosphate Induce Cytokine Generation by Human Mast Cells Through an Interleukin 4-regulated Pathway that Is Inhibited by Leukotriene Receptor Antagonists. JEM 195: 583-592 [Abstract] [Full Text]  


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