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Targeted Disruption of the Leukotriene B4Receptor in Mice Reveals Its Role in Inflammation and Platelet-Activating Factor–Induced Anaphylaxis
Open accessAbstract
Leukotrienes are derived from arachidonic acid and serve as mediators of inflammation and immediate hypersensitivity. Leukotriene B4 (LTB4) and leukotriene C4 (LTC4) act through G protein–coupled receptors LTB4 receptor (BLTR) and Cys-LTR, respectively. To investigate the physiological role of BLTR, we produced mice with a targeted disruption of the BLTR gene. Mice deficient for BLTR (BLTR−/−) developed normally and had no apparent hematopoietic abnormalities. Peritoneal neutrophils from BLTR−/− mice displayed normal responses to the inflammatory mediators C5a and platelet-activating factor (PAF) but did not respond to LTB4 for calcium mobilization or chemotaxis. Additionally, LTB4 elicited peritoneal neutrophil influx in control but not in BLTR−/− mice. Thus, BLTR is the sole receptor for LTB4-induced inflammation in mice. Neutrophil influx in a peritonitis model and acute ear inflammation in response to arachidonic acid was significantly reduced in BLTR−/− mice. In mice, intravenous administration of PAF induces immediate lethal anaphylaxis. Surprisingly, female BLTR−/− mice displayed selective survival (6 of 9; P = 0.002) relative to male (1 of 11) mice of PAF-induced anaphylaxis. These results demonstrate the role of BLTR in leukotriene-mediated acute inflammation and an unexpected sex-related involvement in PAF-induced anaphylaxis.
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The PPARα–leukotriene B4 pathway to inflammation control
Devchand, P. R., Keller, H., Peters, J. M., Vazquez, M., Gonzalez, F. J., & Wahli, W. (1996) · Nature · doi:10.1038/384039a0 · Cited by 1,345
Isoleukotrienes are biologically active free radical products of lipid peroxidation
Harrison, K. A., & Murphy, R. C. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.29.17273 · Cited by 98
Cited by
Lipoxygenase and leukotriene pathways: biochemistry, biology, and roles in disease
Haeggström, J. Z., & Funk, C. D. (2011) · Chemical Reviews · doi:10.1021/cr200246d · Cited by 875
Thematic Review Series: Proteomics. An integrated omics analysis of eicosanoid biology
Buczynski, M. W., Dumlao, D. S., & Dennis, E. A. (2009) · Journal of Lipid Research · doi:10.1194/jlr.r900004-jlr200 · Cited by 530
5-Lipoxygenase, a key enzyme for leukotriene biosynthesis in health and disease
Rådmark, O., Werz, O., Steinhilber, D., & Samuelsson, B. (2015) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2014.08.012 · Cited by 502
Mehrabian, M., Allayee, H., Wong, J., Shih, W., Wang, X.-P., Shaposhnik, Z., Funk, C. D., & Lusis, A. J. (2002) · Circulation Research · doi:10.1161/01.res.0000028008.99774.7f · Cited by 422
BLT1 and BLT2: the leukotriene B4 receptors
Tager, A. M., & Luster, A. D. (2003) · Prostaglandins, Leukotrienes and Essential Fatty Acids · doi:10.1016/s0952-3278(03)00073-5 · Cited by 366
Metadata
- Authors
- Haribabu, B., Verghese, M. W., Steeber, D. A., Sellars, D. D., Bock, C. B., & Snyderman, R.
- Venue
- The Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2000-08-07
- Volume
- 192
- Issue
- 3
- Pages
- 433-438
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- OpenAlex
- W2167243592
- Cited by
- 175
- References
- 2
- FWCI
- 7.02
- Type
- journal article
- Language
- en
- Open access
- green
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- Haribabu, B., Verghese, M. W., Steeber, D. A., Sellars, D. D., Bock, C. B., & Snyderman, R. (2000). Targeted Disruption of the Leukotriene B4Receptor in Mice Reveals Its Role in Inflammation and Platelet-Activating Factor–Induced Anaphylaxis. The Journal of Experimental Medicine. https://doi.org/10.1084/jem.192.3.433
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