| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Laboratory of Molecular Immunology, National, Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892
Activation of phospholipase D (PLD) and protein kinase C (PKC) as well as calcium mobilization are essential signals for degranulation of mast cells. However, the exact role of PLD in degranulation remains undefined. In this study we have tested the hypothesis that the PLD product, phosphatidic acid, and diacylglycerides generated therefrom might promote activation of PKC. Studies were conducted in two rodent mast cell lines that were stimulated with Ag via Fc
RI and a pharmacologic agent, thapsigargin. Diversion of production of phosphatidic acid to phosphatidylbutanol (the transphosphatidylation reaction) by addition of l-butanol suppressed both the translocation of diacylglyceride-dependent isoforms of PKC to the membrane and degranulation. Tertiary-butanol, which is not a substrate for the transphosphatidylation, had a minimal effect on PKC translocation and degranulation, and 1-butanol itself had no effect on PKC translocation when PKC was stimulated directly with phorbol ester, 12-O-tetradecanoylphorbol-13-acetate. Also, in cells transfected with small inhibitory RNAs directed against PLD1 and PLD2, activation of PLD, generation of diacylglycerides, translocation of PKC, and degranulation were all suppressed. Phorbol ester, which did not stimulate degranulation by itself, restored degranulation when used in combination with thapsigargin whether PLD function was disrupted with 1-butanol or the small inhibitory RNAs. However, degranulation was not restored when cells were costimulated with Ag and phorbol ester. These results suggested that the production of phosphatidic acid by PLD facilitates activation of PKC and, in turn, degranulation, although additional PLD-dependent processes appear to be critical for Ag-mediated degranulation.
This article has been cited by other articles:
|
|
 |
|
  M. Zeniou-Meyer, N. Zabari, U. Ashery, S. Chasserot-Golaz, A.-M. Haeberle, V. Demais, Y. Bailly, I. Gottfried, H. Nakanishi, A. M. Neiman, et al. Phospholipase D1 Production of Phosphatidic Acid at the Plasma Membrane Promotes Exocytosis of Large Dense-core Granules at a Late Stage J. Biol. Chem., July 27, 2007; 282(30): 21746 - 21757. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Masuda, K. Hashimoto, T. Yokoi, T. Doi, T. Kodama, H. Kume, K. Ohno, and T. Matsuguchi Essential Role of GATA Transcriptional Factors in the Activation of Mast Cells J. Immunol., January 1, 2007; 178(1): 360 - 368. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. H. Lee, Y. M. Kim, N. W. Kim, J. W. Kim, E. Her, B. K. Kim, J. H. Kim, S. H. Ryu, J. W. Park, D. W. Seo, et al. Phospholipase D2 acts as an essential adaptor protein in the activation of Syk in antigen-stimulated mast cells Blood, August 1, 2006; 108(3): 956 - 964. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. A. Olenchock, R. Guo, M. A. Silverman, J. N. Wu, J. H. Carpenter, G. A. Koretzky, and X.-P. Zhong Impaired degranulation but enhanced cytokine production after Fc{varepsilon}RI stimulation of diacylglycerol kinase {zeta}-deficient mast cells J. Exp. Med., June 12, 2006; 203(6): 1471 - 1480. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
