| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
RI Signaling and to Cytokine and Chemokine Production in Lyn-Deficient Mast Cells1
* Department of Pathology and Cancer Research and Treatment Center, University of New Mexico School of Medicine, Albuquerque, NM 87131;
Lovelace Respiratory Research Institute, Albuquerque, NM 87108; and
Department of Laboratory Medicine, University of California, San Francisco, CA 94143
Cross-linking the high-affinity IgE receptor, Fc
RI, on mast cells activates signaling pathways leading to the release of preformed inflammatory mediators and the production of cytokines and chemokines associated with allergic disorders. Bone marrow-derived mast cells (BMMCs) from Lyn-deficient (Lyn–/–) mice are hyperresponsive to FcRI cross-linking with multivalent Ag. Previous studies linked the hyperresponsive phenotype in part to increased Fyn kinase activity and reduced SHIP phosphatase activity in the Lyn–/– BMMCs in comparison with wild-type (WT) cells. In this study, we compared gene expression profiles between resting and Ag-activated WT and Lyn–/– BMMCs to identify other factors that may contribute to the hyperresponsiveness of the Lyn–/– cells. Among genes implicated in the positive regulation of FcRI signaling, mRNA for the tyrosine kinase, Fyn, and for several proteins contributing to calcium regulation are more up-regulated following Ag stimulation in Lyn–/– BMMCs than in WT BMMCs. Conversely, mRNA for the low-affinity IgG receptor (Fc
RIIB), implicated in negative regulation of FcRI-mediated signaling, is more down-regulated in Ag-stimulated Lyn–/– BMMCs than in WT BMMCs. Genes coding for proinflammatory cytokines and chemokines (IL-4, IL-6, IL-13, CSF, CCL1, CCL3, CCL5, CCL7, CCL9, and MIP1
)are all more highly expressed in Ag-stimulated Lyn–/– mast cells than in WT cells. These microarray data identify Lyn as a negative regulator in Ag-stimulated BMMCs of the expression of genes linked to FcRI signaling and also to the response pathways that lead to allergy and asthma.
This article has been cited by other articles:
|
|
 |
|
  M. P. Nelson, A. E. Metz, S. Li, C. A. Lowell, and C. Steele The Absence of Hck, Fgr, and Lyn Tyrosine Kinases Augments Lung Innate Immune Responses to Pneumocystis murina Infect. Immun., May 1, 2009; 77(5): 1790 - 1797. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Bateman, R. D. Finn, P. J. Sims, T. Wiedmer, A. Biegert, and J. Soding Phospholipid scramblases and Tubby-like proteins belong to a new superfamily of membrane tethered transcription factors Bioinformatics, January 15, 2009; 25(2): 159 - 162. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Amir-Moazami, C. Alexia, N. Charles, P. Launay, R. C. Monteiro, and M. Benhamou Phospholipid Scramblase 1 Modulates a Selected Set of IgE Receptor-mediated Mast Cell Responses through LAT-dependent Pathway J. Biol. Chem., September 12, 2008; 283(37): 25514 - 25523. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. J. Swindle, J. W. Coleman, F. R. DeLeo, and D. D. Metcalfe Fc{epsilon}RI- and Fc{gamma} Receptor-Mediated Production of Reactive Oxygen Species by Mast Cells Is Lipoxygenase- and Cyclooxygenase-Dependent and NADPH Oxidase-Independent J. Immunol., November 15, 2007; 179(10): 7059 - 7071. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Frossi, J. Rivera, E. Hirsch, and C. Pucillo Selective Activation of Fyn/PI3K and p38 MAPK Regulates IL-4 Production in BMMC under Nontoxic Stress Condition J. Immunol., February 15, 2007; 178(4): 2549 - 2555. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
