The Journal of Cell Biology, Vol 116, 635-646, Copyright © 1992 by The Rockefeller University Press

ARTICLES

Binding of monoclonal antibody AA4 to gangliosides on rat basophilic leukemia cells produces changes similar to those seen with Fc epsilon receptor activation

C Oliver, N Sahara, S Kitani, AR Robbins, LM Mertz and RP Siraganian
Laboratory of Immunology, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland 20892.

The mAb AA4 binds to novel derivatives of the ganglioside Gd1b on rat basophilic leukemia (RBL-2H3) cells. Some of the gangliosides are located close to the high affinity IgE receptor (Fc epsilon RI), and binding of mAb AA4 inhibits Fc epsilon RI-mediated histamine release. In the present study, mAb AA4 was found to bind exclusively to mast cells in all rat tissues examined. In vitro, within 1 min of mAb AA4 binding, the cells underwent striking morphologic changes. They lost their normal spindle shaped appearance, increased their ruffling, and spread over the surface of the culture dish. These changes were accompanied by a redistribution of the cytoskeletal elements, actin, tubulin, and vimentin, but only the actin was associated with the membrane ruffles. Binding of mAb AA4 also induces a rise in intracellular calcium, stimulates phosphatidyl inositol breakdown, and activates PKC. However, the extent of these changes was less than that observed when the cells were stimulated with antigen or antibody directed against the Fc epsilon RI. None of these changes associated with mAb AA4 binding were seen when the cells were exposed to nonspecific IgG, IgE, or four other anti-cell surface antibodies, nor were the changes induced by binding mAb AA4 at 4 degrees C or in the absence of extracellular calcium. Although mAb AA4 does not stimulate histamine release, it enhances the effect of the calcium ionophore A23187 mediated release. The morphological and biochemical effects produced by mAb AA4 are similar to those seen following activation of the cell through the IgE receptor. Therefore, the surface gangliosides which bind mAb AA4 may function in modulating secretory events.
CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

• Oliver, C., Fujimura, A., Silveira e Souza, A. M. M., Orlandini de Castro, R., Siraganian, R. P., Jamur, M. C. (2007). Mast Cell-specific Gangliosides and Fc{varepsilon}RI Follow the Same Endocytic Pathway From Lipid Rafts in RBL-2H3 Cells. J. Histochem. Cytochem. 55: 315-325 [Abstract] [Full Text]  
• Geoffrey, R., Jia, S., Kwitek, A. E., Woodliff, J., Ghosh, S., Lernmark, A., Wang, X., Hessner, M. J. (2006). Evidence of a Functional Role for Mast Cells in the Development of Type 1 Diabetes Mellitus in the BioBreeding Rat. J. Immunol. 177: 7275-7286 [Abstract] [Full Text]  
• Jamur, M. C., Grodzki, A. C. G., Berenstein, E. H., Hamawy, M. M., Siraganian, R. P., Oliver, C. (2005). Identification and characterization of undifferentiated mast cells in mouse bone marrow. Blood 105: 4282-4289 [Abstract] [Full Text]  
• Vial, D., Oliver, C., Jamur, M. C., Pastor, M. V. D., da Silva Trindade, E., Berenstein, E., Zhang, J., Siraganian, R. P. (2003). Alterations in Granule Matrix and Cell Surface of Focal Adhesion Kinase-Deficient Mast Cells. J. Immunol. 171: 6178-6186 [Abstract] [Full Text]  
• Martin-Verdeaux, S., Pombo, I., Iannascoli, B., Roa, M., Varin-Blank, N., Rivera, J., Blank, U. (2003). Evidence of a role for Munc18-2 and microtubules in mast cell granule exocytosis. J. Cell Sci. 116: 325-334 [Abstract] [Full Text]  
• Jamur, M. C., Grodzki, A. C. G., Moreno, A. N., de Fátima C. de Mello, L., Pastor, M. V. D., Berenstein, E. H., Siraganian, R. P., Oliver, C. (2001). Identification and Isolation of Rat Bone Marrow-derived Mast Cells Using the Mast Cell-specific Monoclonal Antibody AA4. J. Histochem. Cytochem. 49: 219-228 [Abstract] [Full Text]  
• Field, K. A., Apgar, J. R., Hong-Geller, E., Siraganian, R. P., Baird, B., Holowka, D. (2000). Mutant RBL Mast Cells Defective in Fcepsilon RI Signaling and Lipid Raft Biosynthesis Are Reconstituted by Activated Rho-family GTPases. Mol. Biol. Cell 11: 3661-3673 [Abstract] [Full Text]  
• Prieschl, E. E., Csonga, R., Novotny, V., Kikuchi, G. E., Baumruker, T. (2000). Glycosphingolipid-Induced Relocation of Lyn and Syk into Detergent-Resistant Membranes Results in Mast Cell Activation. J. Immunol. 164: 5389-5397 [Abstract] [Full Text]  
• Draberova, L., Draberova, E., Surviladze, Z., Draber, P., Draber, P. (1999). Protein tyrosine kinase p53/p56lyn forms complexes with {gamma}-tubulin in rat basophilic leukemia cells. Int Immunol 11: 1829-1839 [Abstract] [Full Text]  
• Field, K. A., Holowka, D., Baird, B. (1999). Structural Aspects of the Association of Fcepsilon RI with Detergent-resistant Membranes. J. Biol. Chem. 274: 1753-1758 [Abstract] [Full Text]  
• Stauffer, T. P., Meyer, T. (1997). Compartmentalized IgE Receptor-mediated Signal Transduction in Living Cells. JCB 139: 1447-1454 [Abstract] [Full Text]  
• Jamur, M. C., Grodzki, A. C. G., Moreno, A. N., Swaim, W. D., Siraganian, R. P., Oliver, C. (1997). Immunomagnetic Isolation of Rat Bone Marrow-derived and Peritoneal Mast Cells. J. Histochem. Cytochem. 45: 1715-1722 [Abstract] [Full Text]  
• Kasahara, K., Watanabe, Y., Yamamoto, T., Sanai, Y. (1997). Association of Src Family Tyrosine Kinase Lyn with Ganglioside GD3 in Rat Brain. POSSIBLE REGULATION OF Lyn BY GLYCOSPHINGOLIPID IN CAVEOLAE-LIKE DOMAINS. J. Biol. Chem. 272: 29947-29953 [Abstract] [Full Text]  
• Dai, J., Ting-Beall, H. P., Sheetz, M. P. (1997). The Secretion-coupled Endocytosis Correlates with Membrane Tension Changes in RBL 2H3 Cells. JGP 110: 1-10 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents