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Impaired degranulation but enhanced cytokine production after Fc epsilonRI stimulation of diacylglycerol kinase zeta-deficient mast cells.

Publication ,  Journal Article
Olenchock, BA; Guo, R; Silverman, MA; Wu, JN; Carpenter, JH; Koretzky, GA; Zhong, X-P
Published in: J Exp Med
June 12, 2006

Calcium and diacylglycerol are critical second messengers that together effect mast cell degranulation after allergen cross-linking of immunoglobulin (Ig)E-bound FcepsilonRI. Diacylglycerol kinase (DGK)zeta is a negative regulator of diacylglycerol-dependent signaling that acts by converting diacylglycerol to phosphatidic acid. We reported previously that DGKzeta-/- mice have enhanced in vivo T cell function. Here, we demonstrate that these mice have diminished in vivo mast cell function, as revealed by impaired local anaphylactic responses. Concordantly, DGKzeta-/- bone marrow-derived mast cells (BMMCs) demonstrate impaired degranulation after Fc epsilonRI cross-linking, associated with diminished phospholipase Cgamma activity, calcium flux, and protein kinase C-betaII membrane recruitment. In contrast, Ras-Erk signals and interleukin-6 production are enhanced, both during IgE sensitization and after antigen cross-linking of Fc epsilonRI. Our data demonstrate dissociation between cytokine production and degranulation in mast cells and reveal the importance of DGK activity during IgE sensitization for proper attenuation of Fc epsilonRI signals.

Duke Scholars

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Published In

J Exp Med

DOI

ISSN

0022-1007

Publication Date

June 12, 2006

Volume

203

Issue

6

Start / End Page

1471 / 1480

Location

United States

Related Subject Headings

  • Receptors, IgE
  • Polymerase Chain Reaction
  • Passive Cutaneous Anaphylaxis
  • Mice, Knockout
  • Mice
  • Mast Cells
  • Interleukin-6
  • Immunology
  • Flow Cytometry
  • Diacylglycerol Kinase
 

Citation

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Chicago
ICMJE
MLA
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Olenchock, B. A., Guo, R., Silverman, M. A., Wu, J. N., Carpenter, J. H., Koretzky, G. A., & Zhong, X.-P. (2006). Impaired degranulation but enhanced cytokine production after Fc epsilonRI stimulation of diacylglycerol kinase zeta-deficient mast cells. J Exp Med, 203(6), 1471–1480. https://doi.org/10.1084/jem.20052424
Olenchock, Benjamin A., Rishu Guo, Michael A. Silverman, Jennifer N. Wu, Jeffery H. Carpenter, Gary A. Koretzky, and Xiao-Ping Zhong. “Impaired degranulation but enhanced cytokine production after Fc epsilonRI stimulation of diacylglycerol kinase zeta-deficient mast cells.J Exp Med 203, no. 6 (June 12, 2006): 1471–80. https://doi.org/10.1084/jem.20052424.
Olenchock BA, Guo R, Silverman MA, Wu JN, Carpenter JH, Koretzky GA, et al. Impaired degranulation but enhanced cytokine production after Fc epsilonRI stimulation of diacylglycerol kinase zeta-deficient mast cells. J Exp Med. 2006 Jun 12;203(6):1471–80.
Olenchock, Benjamin A., et al. “Impaired degranulation but enhanced cytokine production after Fc epsilonRI stimulation of diacylglycerol kinase zeta-deficient mast cells.J Exp Med, vol. 203, no. 6, June 2006, pp. 1471–80. Pubmed, doi:10.1084/jem.20052424.
Olenchock BA, Guo R, Silverman MA, Wu JN, Carpenter JH, Koretzky GA, Zhong X-P. Impaired degranulation but enhanced cytokine production after Fc epsilonRI stimulation of diacylglycerol kinase zeta-deficient mast cells. J Exp Med. 2006 Jun 12;203(6):1471–1480.

Published In

J Exp Med

DOI

ISSN

0022-1007

Publication Date

June 12, 2006

Volume

203

Issue

6

Start / End Page

1471 / 1480

Location

United States

Related Subject Headings

  • Receptors, IgE
  • Polymerase Chain Reaction
  • Passive Cutaneous Anaphylaxis
  • Mice, Knockout
  • Mice
  • Mast Cells
  • Interleukin-6
  • Immunology
  • Flow Cytometry
  • Diacylglycerol Kinase