SLP-76 deficiency impairs signaling via the high-affinity IgE receptor in mast cells
| Autor: | V I, Pivniouk, T R, Martin, J M, Lu-Kuo, H R, Katz, H C, Oettgen, R S, Geha |
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| Rok vydání: | 1999 |
| Předmět: |
Mice
Knockout Binding Sites genetic structures Receptors IgE Passive Cutaneous Anaphylaxis Bone Marrow Cells Cell Differentiation Mice Inbred Strains Immunoglobulin E equipment and supplies Phosphoproteins Adoptive Transfer eye diseases Cell Degranulation Article Mice Animals Cytokines sense organs Mast Cells Cells Cultured Adaptor Proteins Signal Transducing Signal Transduction |
| Zdroj: | The Journal of clinical investigation. 103(12) |
| ISSN: | 0021-9738 |
| Popis: | SLP-76 is an adapter protein expressed in T cells and myeloid cells that is a substrate for ZAP-70 and Syk. SLP-76-deficient mice exhibit a profound block in T-cell development. We found that although SLP-76 is expressed in mouse mast cells, SLP-76(-/-) mice have normal numbers of mast cells in their skin and bronchi. SLP-76(-/-) mice are resistant to IgE-mediated passive anaphylaxis. SLP-76(-/-) mice sensitized with IgE anti-dinitrophenyl (DNP) and then challenged with DNP-HSA developed only mild and transient tachycardia, failed to increase their plasma histamine level, and all survived the antigen challenge. Bone marrow-derived mast cells (BMMCs) from SLP76(-/-) mice failed to release beta-hexosaminidase and to secrete IL-6 after FcepsilonRI cross-linking. Tyrosine phosphorylation of phospholipase C-gamma1 (but not of Syk) and calcium mobilization in response to IgE cross-linking were reduced in SLP-76-deficient BMMCs. These results suggest that SLP-76 plays an important role in FcepsilonRI-mediated signaling in mast cells. |
| Databáze: | OpenAIRE |
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