SWAP-70-deficient mast cells are impaired in development and IgE-mediated degranulation.
Cross-linking of the high-affinity IgE receptor (FcepsilonRI) on mast cell activates signaling pathways that trigger degranulation and the release of multiple pro-inflammatory mediators. Mature,immature and precursor mast cells are degranulation competent. We show here that the signaling protein SWAP-70 has a function in mast cell biology. While not found in many cell types, we find that apart from B cells, mast cells also express SWAP-70. In activated B cells, SWAP-70 shuttles between cytoplasm and nucleus, but in mast cells it is confined to the cytoplasm. SWAP-70(ko/ko) (double knockout) mice have reduced numbers of mature mast cells, and these are degranulation competent. However, although immature mast cells from SWAP-70(ko/ko) mice respond normally to SCF and IL-3 and have functional granules, their FcepsilonRI-mediated degranulation is inhibited. Thus, in mast cells SWAP-70 plays a role both in establishing the initial competence to degranulate and to develop into mature mast cells.
Gross
Brigitte
B
Basel Institute for Immunology, Basel, Switzerland.
Borggrefe
Tilman
T
Wabl
Matthias
M
Sivalenka
Raja Rajeswari
RR
Bennett
Mark
M
Rossi
Alexander B
AB
Jessberger
Rolf
R
D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism; D002454:Cell Differentiation; D003593:Cytoplasm / Q000378:metabolism; D003594:Cytoplasmic Granules / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D005089:Exocytosis / Q000187:drug effects / Q000502:physiology*; D020662:Guanine Nucleotide Exchange Factors; D007073:Immunoglobulin E / Q000276:immunology*; D007377:Interleukin-3 / Q000494:pharmacology; D008407:Mast Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D015778:Minor Histocompatibility Antigens; D009687:Nuclear Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D017455:Receptors, IgE / Q000276:immunology; D015398:Signal Transduction; D019089:Stem Cell Factor / Q000494:pharmacology
D004268:DNA-Binding Proteins; D020662:Guanine Nucleotide Exchange Factors; D007377:Interleukin-3; D015778:Minor Histocompatibility Antigens; D009687:Nuclear Proteins; D017455:Receptors, IgE; D019089:Stem Cell Factor; C113365:Swap70 protein, mouse; D007073:Immunoglobulin E