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Involvement of Bruton's Tyrosine Kinase in FcεRI-dependent Mast Cell Degranulation and Cytokine Production
- Source :
- The Journal of Experimental Medicine
- Publication Year :
- 1998
- Publisher :
- The Rockefeller University Press, 1998.
-
Abstract
- We investigated the role of Bruton's tyrosine kinase (Btk) in FcepsilonRI-dependent activation of mouse mast cells, using xid and btk null mutant mice. Unlike B cell development, mast cell development is apparently normal in these btk mutant mice. However, mast cells derived from these mice exhibited significant abnormalities in FcepsilonRI-dependent function. xid mice primed with anti-dinitrophenyl monoclonal IgE antibody exhibited mildly diminished early-phase and severely blunted late-phase anaphylactic reactions in response to antigen challenge in vivo. Consistent with this finding, cultured mast cells derived from the bone marrow cells of xid or btk null mice exhibited mild impairments in degranulation, and more profound defects in the production of several cytokines, upon FcepsilonRI cross-linking. Moreover, the transcriptional activities of these cytokine genes were severely reduced in FcepsilonRI-stimulated btk mutant mast cells. The specificity of these effects of btk mutations was confirmed by the improvement in the ability of btk mutant mast cells to degranulate and to secrete cytokines after the retroviral transfer of wild-type btk cDNA, but not of vector or kinase-dead btk cDNA. Retroviral transfer of Emt (= Itk/Tsk), Btk's closest relative, also partially improved the ability of btk mutant mast cells to secrete mediators. Taken together, these results demonstrate an important role for Btk in the full expression of FcepsilonRI signal transduction in mast cells.
- Subjects :
- medicine.medical_treatment
Immunology
Bone Marrow Cells
Immunoglobulin E
Histamine Release
Models, Biological
Article
Cell Degranulation
03 medical and health sciences
Mice
0302 clinical medicine
immune system diseases
hemic and lymphatic diseases
medicine
Agammaglobulinaemia Tyrosine Kinase
Immunology and Allergy
Bruton's tyrosine kinase
Animals
Mast Cells
B cell
030304 developmental biology
0303 health sciences
biology
Receptors, IgE
Passive Cutaneous Anaphylaxis
Degranulation
Articles
Protein-Tyrosine Kinases
Mast cell
Mice, Mutant Strains
Recombinant Proteins
3. Good health
Cell biology
medicine.anatomical_structure
Cytokine
Gene Expression Regulation
biology.protein
Cytokines
Antibody
Tyrosine kinase
030215 immunology
Signal Transduction
Subjects
Details
- Language :
- English
- ISSN :
- 15409538 and 00221007
- Volume :
- 187
- Issue :
- 8
- Database :
- OpenAIRE
- Journal :
- The Journal of Experimental Medicine
- Accession number :
- edsair.doi.dedup.....4c8aa584787da86fa7683c3a840b01c3