Brief Definitive Report

BLTR Mediates Leukotriene B₄–induced Chemotaxis and Adhesion and Plays a Dominant Role in Eosinophil Accumulation in a Murine Model of Peritonitis

Correspondence to: Andrew D. Luster, Massachusetts General Hospital, Bldg. 149, 13th St., Charlestown, MA 02129. Tel:617-726-5710 Fax:617-726-5411 E-mail:luster{at}helix.mgh.harvard.edu.

Leukotriene B₄ (LTB₄) is a potent chemoattractant active on multiple leukocytes, including neutrophils, macrophages, and eosinophils, and is implicated in the pathogenesis of a variety of inflammatory processes. A seven transmembrane–spanning, G protein–coupled receptor, called BLTR (LTB₄ receptor), has recently been identified as an LTB₄ receptor. To determine if BLTR is the sole receptor mediating LTB₄-induced leukocyte activation and to determine the role of LTB₄ and BLTR in regulating leukocyte function in inflammation in vivo, we generated a BLTR-deficient mouse by targeted gene disruption. This mouse reveals that BLTR alone is responsible for LTB₄-mediated leukocyte calcium flux, chemotaxis, and firm adhesion to endothelium in vivo. Furthermore, despite the apparent functional redundancy with other chemoattractant–receptor pairs in vitro, LTB₄ and BLTR play an important role in the recruitment and/or retention of leukocytes, particularly eosinophils, to the inflamed peritoneum in vivo. These studies demonstrate that BLTR is the key receptor that mediates LTB₄-induced leukocyte activation and establishes a model to decipher the functional roles of BLTR and LTB₄ in vivo.

Key Words: receptors, leukotriene, chemotactic factors, inflammation mediators, knockout

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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]  
• King, V. L., Lin, A. Y., Kristo, F., Anderson, T. J.T., Ahluwalia, N., Hardy, G. J., Owens, A. P. III, Howatt, D. A., Shen, D., Tager, A. M., Luster, A. D., Daugherty, A., Gerszten, R. E. (2009). Interferon-{gamma} and the Interferon-Inducible Chemokine CXCL10 Protect Against Aneurysm Formation and Rupture. Circulation 119: 426-435 [Abstract] [Full Text]  
• Medeiros, A. I., Sa-Nunes, A., Turato, W. M., Secatto, A., Frantz, F. G., Sorgi, C. A., Serezani, C. H., Deepe, G. S. Jr., Faccioli, L. H. (2008). Leukotrienes Are Potent Adjuvant during Fungal Infection: Effects on Memory T Cells. J. Immunol. 181: 8544-8551 [Abstract] [Full Text]  
• Munitz, A., McBride, M. L., Bernstein, J. S., Rothenberg, M. E. (2008). A dual activation and inhibition role for the paired immunoglobulin-like receptor B in eosinophils. Blood 111: 5694-5703 [Abstract] [Full Text]  
• Reichel, C. A., Rehberg, M., Bihari, P., Moser, C. M., Linder, S., Khandoga, A., Krombach, F. (2008). Gelatinases mediate neutrophil recruitment in vivo: evidence for stimulus specificity and a critical role in collagen IV remodeling. J. Leukoc. Biol. 83: 864-874 [Abstract] [Full Text]  
• Jacobsen, E. A., Ochkur, S. I., Pero, R. S., Taranova, A. G., Protheroe, C. A., Colbert, D. C., Lee, N. A., Lee, J. J. (2008). Allergic pulmonary inflammation in mice is dependent on eosinophil-induced recruitment of effector T cells. JEM 205: 699-710 [Abstract] [Full Text]  
• Narushima, S., DiMeo, D., Tian, J., Zhang, J., Liu, D., Berg, D. J. (2008). 5-Lipoxygenase-derived lipid mediators are not required for the development of NSAID-induced inflammatory bowel disease in IL-10-/- mice. Am. J. Physiol. Gastrointest. Liver Physiol. 294: G477-G488 [Abstract] [Full Text]  
• Woodfin, A., Reichel, C. A., Khandoga, A., Corada, M., Voisin, M.-B., Scheiermann, C., Haskard, D. O., Dejana, E., Krombach, F., Nourshargh, S. (2007). JAM-A mediates neutrophil transmigration in a stimulus-specific manner in vivo: evidence for sequential roles for JAM-A and PECAM-1 in neutrophil transmigration. Blood 110: 1848-1856 [Abstract] [Full Text]  
• Ahluwalia, N., Lin, A. Y., Tager, A. M., Pruitt, I. E., Anderson, T. J. T., Kristo, F., Shen, D., Cruz, A. R., Aikawa, M., Luster, A. D., Gerszten, R. E. (2007). Inhibited Aortic Aneurysm Formation in BLT1-Deficient Mice. J. Immunol. 179: 691-697 [Abstract] [Full Text]  
• Arita, M., Ohira, T., Sun, Y.-P., Elangovan, S., Chiang, N., Serhan, C. N. (2007). Resolvin E1 Selectively Interacts with Leukotriene B4 Receptor BLT1 and ChemR23 to Regulate Inflammation. J. Immunol. 178: 3912-3917 [Abstract] [Full Text]  
• Kelly, K. A., Allport, J. R., Yu, A. M., Sinh, S., Sage, E. H., Gerszten, R. E., Weissleder, R. (2007). SPARC is a VCAM-1 counter-ligand that mediates leukocyte transmigration. J. Leukoc. Biol. 81: 748-756 [Abstract] [Full Text]  
• Heller, E. A., Liu, E., Tager, A. M., Yuan, Q., Lin, A. Y., Ahluwalia, N., Jones, K., Koehn, S. L., Lok, V. M., Aikawa, E., Moore, K. J., Luster, A. D., Gerszten, R. E. (2006). Chemokine CXCL10 Promotes Atherogenesis by Modulating the Local Balance of Effector and Regulatory T Cells. Circulation 113: 2301-2312 [Abstract] [Full Text]  
• Kim, N. D., Chou, R. C., Seung, E., Tager, A. M., Luster, A. D. (2006). A unique requirement for the leukotriene B4 receptor BLT1 for neutrophil recruitment in inflammatory arthritis. JEM 203: 829-835 [Abstract] [Full Text]  
• Taube, C., Miyahara, N., Ott, V., Swanson, B., Takeda, K., Loader, J., Shultz, L. D., Tager, A. M., Luster, A. D., Dakhama, A., Gelfand, E. W. (2006). The Leukotriene B4 Receptor (BLT1) Is Required for Effector CD8+ T Cell-Mediated, Mast Cell-Dependent Airway Hyperresponsiveness.. J. Immunol. 176: 3157-3164 [Abstract] [Full Text]  
• Medoff, B. D., Tager, A. M., Jackobek, R., Means, T. K., Wang, L., Luster, A. D. (2006). Antibody-antigen interaction in the airway drives early granulocyte recruitment through BLT1. Am. J. Physiol. Lung Cell. Mol. Physiol. 290: L170-L178 [Abstract] [Full Text]  
• Mallia, P., Johnston, S. L. (2005). Mechanisms and Experimental Models of Chronic Obstructive Pulmonary Disease Exacerbations. Proc Am Thorac Soc 2: 361-366 [Abstract] [Full Text]  
• Terawaki, K., Yokomizo, T., Nagase, T., Toda, A., Taniguchi, M., Hashizume, K., Yagi, T., Shimizu, T. (2005). Absence of Leukotriene B4 Receptor 1 Confers Resistance to Airway Hyperresponsiveness and Th2-Type Immune Responses. J. Immunol. 175: 4217-4225 [Abstract] [Full Text]  
• Okuno, T., Yokomizo, T., Hori, T., Miyano, M., Shimizu, T. (2005). Leukotriene B4 Receptor and the Function of Its Helix 8. J. Biol. Chem. 280: 32049-32052 [Abstract] [Full Text]  
• Caironi, P., Ichinose, F., Liu, R., Jones, R. C., Bloch, K. D., Zapol, W. M. (2005). 5-Lipoxygenase Deficiency Prevents Respiratory Failure during Ventilator-induced Lung Injury. Am. J. Respir. Crit. Care Med. 172: 334-343 [Abstract] [Full Text]  
• Heller, E. A., Liu, E., Tager, A. M., Sinha, S., Roberts, J. D., Koehn, S. L., Libby, P., Aikawa, E. R., Chen, J. Q., Huang, P., Freeman, M. W., Moore, K. J., Luster, A. D., Gerszten, R. E. (2005). Inhibition of Atherogenesis in BLT1-Deficient Mice Reveals a Role for LTB4 and BLT1 in Smooth Muscle Cell Recruitment. Circulation 112: 578-586 [Abstract] [Full Text]  
• Medoff, B. D., Seung, E., Wain, J. C., Means, T. K., Campanella, G. S.V., Islam, S. A., Thomas, S. Y., Ginns, L. C., Grabie, N., Lichtman, A. H., Tager, A. M., Luster, A. D. (2005). BLT1-mediated T cell trafficking is critical for rejection and obliterative bronchiolitis after lung transplantation. JEM 202: 97-110 [Abstract] [Full Text]  
• Sabirsh, A., Wetterholm, A., Bristulf, J., Leffler, H., Haeggstrom, J. Z., Owman, C. (2005). Fluorescent leukotriene B4: potential applications. J. Lipid Res. 46: 1339-1346 [Abstract] [Full Text]  
• Miyahara, N., Takeda, K., Miyahara, S., Taube, C., Joetham, A., Koya, T., Matsubara, S., Dakhama, A., Tager, A. M., Luster, A. D., Gelfand, E. W. (2005). Leukotriene B4 Receptor-1 Is Essential for Allergen-Mediated Recruitment of CD8+ T Cells and Airway Hyperresponsiveness. J. Immunol. 174: 4979-4984 [Abstract] [Full Text]  
• Haeggstrom, J. Z. (2004). Leukotriene A4 Hydrolase/Aminopeptidase, the Gatekeeper of Chemotactic Leukotriene B4 Biosynthesis. J. Biol. Chem. 279: 50639-50642 [Full Text]  
• Scott, M. J., Cheadle, W. G., Hoth, J. J., Peyton, J. C., Subbarao, K., Shao, W.-H., Haribabu, B. (2004). Leukotriene B4 Receptor (BLT-1) Modulates Neutrophil Influx into the Peritoneum but Not the Lung and Liver during Surgically Induced Bacterial Peritonitis in Mice. CVI 11: 936-941 [Abstract] [Full Text]  
• Puri, K. D., Doggett, T. A., Douangpanya, J., Hou, Y., Tino, W. T., Wilson, T., Graf, T., Clayton, E., Turner, M., Hayflick, J. S., Diacovo, T. G. (2004). Mechanisms and implications of phosphoinositide 3-kinase {delta} in promoting neutrophil trafficking into inflamed tissue. Blood 103: 3448-3456 [Abstract] [Full Text]  
• Subbarao, K., Jala, V. R., Mathis, S., Suttles, J., Zacharias, W., Ahamed, J., Ali, H., Tseng, M. T., Haribabu, B. (2004). Role of Leukotriene B4 Receptors in the Development of Atherosclerosis: Potential Mechanisms. Arterioscler. Thromb. Vasc. Bio. 24: 369-375 [Abstract] [Full Text]  
• Okuno, T., Ago, H., Terawaki, K., Miyano, M., Shimizu, T., Yokomizo, T. (2003). Helix 8 of the Leukotriene B4 Receptor Is Required for the Conformational Change to the Low Affinity State after G-protein Activation. J. Biol. Chem. 278: 41500-41509 [Abstract] [Full Text]  
• Myou, S., Leff, A. R., Myo, S., Boetticher, E., Meliton, A. Y., Lambertino, A. T., Liu, J., Xu, C., Munoz, N. M., Zhu, X. (2003). Activation of Group IV Cytosolic Phospholipase A2 in Human Eosinophils by Phosphoinositide 3-Kinase Through a Mitogen-Activated Protein Kinase-Independent Pathway. J. Immunol. 171: 4399-4405 [Abstract] [Full Text]  
• Yopp, A. C., Randolph, G. J., Bromberg, J. S. (2003). Leukotrienes, Sphingolipids, and Leukocyte Trafficking. J. Immunol. 171: 5-10 [Full Text]  
• Brink, C., Dahlen, S.-E., Drazen, J., Evans, J. F., Hay, D. W. P., Nicosia, S., Serhan, C. N., Shimizu, T., Yokomizo, T. (2003). International Union of Pharmacology XXXVII. Nomenclature for Leukotriene and Lipoxin Receptors. Pharmacol. Rev. 55: 195-227 [Abstract] [Full Text]  
• Gaudreau, R., Le Gouill, C., Venne, M.-H., Stankova, J., Rola-Pleszczynski, M. (2002). Threonine 308 within a Putative Casein Kinase 2 Site of the Cytoplasmic Tail of Leukotriene B4 Receptor (BLT1) Is Crucial for Ligand-induced, G-protein-coupled Receptor-specific Kinase 6-mediated Desensitization. J. Biol. Chem. 277: 31567-31576 [Abstract] [Full Text]  
• Mehrabian, M., Allayee, H., Wong, J., Shih, W., Wang, X.-P., Shaposhnik, Z., Funk, C. D., Lusis, A. J. (2002). Identification of 5-Lipoxygenase as a Major Gene Contributing to Atherosclerosis Susceptibility in Mice. Circ. Res. 91: 120-126 [Abstract] [Full Text]  
• Stankova, J., Turcotte, S., Harris, J., Rola-Pleszczynski, M. (2002). Modulation of Leukotriene B4 Receptor-1 Expression by Dexamethasone: Potential Mechanism for Enhanced Neutrophil Survival. J. Immunol. 168: 3570-3576 [Abstract] [Full Text]  
• Woo, C.-H., You, H.-J., Cho, S.-H., Eom, Y.-W., Chun, J.-S., Yoo, Y.-J., Kim, J.-H. (2002). Leukotriene B4 Stimulates Rac-ERK Cascade to Generate Reactive Oxygen Species That Mediates Chemotaxis. J. Biol. Chem. 277: 8572-8578 [Abstract] [Full Text]  
• Dawkins, P A, Stockley, R A (2001). Animal models of chronic obstructive pulmonary disease. Thorax 56: 972-977 [Full Text]  
• Serhan, C. N., Prescott, S. M. (2000). The Scent of a Phagocyte: Advances on Leukotriene B4 Receptors. JEM 192: F5-F8 [Abstract] [Full Text]  
• Ichinose, F., Zapol, W. M., Sapirstein, A., Ullrich, R., Tager, A. M., Coggins, K., Jones, R., Bloch, K. D. (2001). Attenuation of Hypoxic Pulmonary Vasoconstriction by Endotoxemia Requires 5-Lipoxygenase in Mice. Circ. Res. 88: 832-838 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS