Brief Definitive Report

Increased Severity of Local and Systemic Anaphylactic Reactions in gp49B1-deficient Mice

Correspondence to: Howard R. Katz, Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, 1 Jimmy Fund Way, Rm. 638A, Boston, MA 02115. Tel:617-525-1307 Fax:617-525-1308 E-mail:hrkatz{at}mbcrr.harvard.edu.

gp49B1 is an immunoglobulin (Ig) superfamily member that inhibits FcRI-induced mast cell activation when the two receptors are coligated with antibodies in vitro. The critical question of in vivo function of gp49B1 is now addressed in gene-disrupted mice. gp49B1-deficient mice exhibited a significantly increased sensitivity to IgE-dependent passive cutaneous anaphylaxis as assessed by greater tissue swelling and mast cell degranulation in situ. Importantly, by the same criteria, the absence of gp49B1 also resulted in a lower threshold for antigen challenge in active cutaneous anaphylaxis, in which the antigen-specific antibody levels were comparable in gp49B1-deficient and sufficient mice. Moreover, the absence of gp49B1 resulted in a significantly greater and faster death rate in active systemic anaphylaxis. These results indicate that gp49B1 innately dampens adaptive immediate hypersensitivity responses by suppressing mast cell activation in vivo. In addition, this study provides a new concept and target for regulation of allergic disease susceptibility and severity.

Key Words: mast cells, immunoreceptor tyrosine-based inhibitory motif, passive cutaneous anaphylaxis, active cutaneous anaphylaxis, active systemic anaphylaxis

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

This article has been cited by other articles:

• Maekawa, A., Kanaoka, Y., Xing, W., Austen, K. F. (2008). Functional recognition of a distinct receptor preferential for leukotriene E4 in mice lacking the cysteinyl leukotriene 1 and 2 receptors. Proc. Natl. Acad. Sci. USA 105: 16695-16700 [Abstract] [Full Text]  
• Norris, H. H., Peterson, M. E., Stebbins, C. C., McConchie, B. W., Bundoc, V. G., Trivedi, S., Hodges, M. G., Anthony, R. M., Urban, J. F. Jr, Long, E. O., Keane-Myers, A. M. (2007). Inhibitory receptor gp49B regulates eosinophil infiltration during allergic inflammation. J. Leukoc. Biol. 82: 1531-1541 [Abstract] [Full Text]  
• Zhou, J. S., Xing, W., Friend, D. S., Austen, K. F., Katz, H. R. (2007). Mast cell deficiency in KitW-sh mice does not impair antibody-mediated arthritis. JEM 204: 2797-2802 [Abstract] [Full Text]  
• Masuda, A., Nakamura, A., Maeda, T., Sakamoto, Y., Takai, T. (2007). Cis binding between inhibitory receptors and MHC class I can regulate mast cell activation. JEM 204: 907-920 [Abstract] [Full Text]  
• Iida, S., Kohro, T., Kodama, T., Nagata, S., Fukunaga, R. (2005). Identification of CCR2, flotillin, and gp49B genes as new G-CSF targets during neutrophilic differentiation. J. Leukoc. Biol. 78: 481-490 [Abstract] [Full Text]  
• Knoops, L., Louahed, J., Van Snick, J., Renauld, J.-C. (2005). IL-9 Promotes but Is Not Necessary for Systemic Anaphylaxis. J. Immunol. 175: 335-341 [Abstract] [Full Text]  
• Cherwinski, H. M., Murphy, C. A., Joyce, B. L., Bigler, M. E., Song, Y. S., Zurawski, S. M., Moshrefi, M. M., Gorman, D. M., Miller, K. L., Zhang, S., Sedgwick, J. D., Phillips, J. H. (2005). The CD200 Receptor Is a Novel and Potent Regulator of Murine and Human Mast Cell Function. J. Immunol. 174: 1348-1356 [Abstract] [Full Text]  
• Sloane, D. E., Tedla, N., Awoniyi, M., MacGlashan, D. W. Jr, Borges, L., Austen, K. F., Arm, J. P. (2004). Leukocyte immunoglobulin-like receptors: novel innate receptors for human basophil activation and inhibition. Blood 104: 2832-2839 [Abstract] [Full Text]  
• Zhou, J. S., Friend, D. S., Feldweg, A. M., Daheshia, M., Li, L., Austen, K. F., Katz, H. R. (2003). Prevention of Lipopolysaccharide-induced Microangiopathy by gp49B1: Evidence for an Important Role for gp49B1 Expression on Neutrophils. JEM 198: 1243-1251 [Abstract] [Full Text]  
• Gu, X., Laouar, A., Wan, J., Daheshia, M., Lieberman, J., Yokoyama, W. M., Katz, H. R., Manjunath, N. (2003). The gp49B1 Inhibitory Receptor Regulates the IFN-{gamma} Responses of T Cells and NK Cells. J. Immunol. 170: 4095-4101 [Abstract] [Full Text]  
• Tedla, N., Bandeira-Melo, C., Tassinari, P., Sloane, D. E., Samplaski, M., Cosman, D., Borges, L., Weller, P. F., Arm, J. P. (2003). Activation of human eosinophils through leukocyte immunoglobulin-like receptor 7. Proc. Natl. Acad. Sci. USA 100: 1174-1179 [Abstract] [Full Text]  
• Migliaccio, A. R., Rana, R. A., Sanchez, M., Lorenzini, R., Centurione, L., Bianchi, L., Vannucchi, A. M., Migliaccio, G., Orkin, S. H. (2003). GATA-1 as a Regulator of Mast Cell Differentiation Revealed by the Phenotype of the GATA-1low Mouse Mutant. JEM 197: 281-296 [Abstract] [Full Text]  
• Wong, M.-X., Roberts, D., Bartley, P. A., Jackson, D. E. (2002). Absence of Platelet Endothelial Cell Adhesion Molecule-1 (CD31) Leads to Increased Severity of Local and Systemic IgE-Mediated Anaphylaxis and Modulation of Mast Cell Activation. J. Immunol. 168: 6455-6462 [Abstract] [Full Text]  
• Tedla, N., Gibson, K., McNeil, H. P., Cosman, D., Borges, L., Arm, J. P. (2002). The Co-Expression of Activating and Inhibitory Leukocyte Immunoglobulin-Like Receptors in Rheumatoid Synovium. Am. J. Pathol. 160: 425-431 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS