HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hernandez-Hansen, V. Articles by Oliver, J. M. Search for Related Content PubMed PubMed Citation Articles by Hernandez-Hansen, V. Articles by Oliver, J. M.

Increased Expression of Genes Linked to FcRI Signaling and to Cytokine and Chemokine Production in Lyn-Deficient Mast Cells¹

Valerie Hernandez-Hansen^2,*, Julie D. J. Bard^*, Christy A. Tarleton^*, Julie A. Wilder, Clifford A. Lowell, Bridget S. Wilson^* and Janet M. Oliver^3,*

^* 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, FcRI, 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 (FcRIIB), 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:

				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]