PMID- 15542585
OWN - NLM
STAT- MEDLINE
DCOM- 20050324
LR  - 20210206
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 105
IP  - 5
DP  - 2005 Mar 1
TI  - Rapid and large amount of autocrine IL-3 production is responsible for mast cell 
      survival by IgE in the absence of antigen.
PG  - 2059-65
AB  - Cross-linking FcepsilonRI on mast cells by immunoglobulin E (IgE) and antigen 
      (Ag) initiates cascades leading to antiparasitic or allergic responses. It was 
      recently reported that IgE without antigen, IgE(-Ag), actively promotes mast cell 
      survival. Although we have demonstrated that the immunoreceptor tyrosine-based 
      activation motif within FcRgamma is essential for IgE(-Ag)-induced mast cell 
      survival, the underlying mechanism remains still unclear. Here, we investigated 
      the mechanism of IgE(-Ag)-induced survival using mast cells lacking several 
      downstream molecules. Lyn and Syk were essential, whereas Fyn, Gab2, and the 
      phosphoinositide 3-kinase-Akt pathway were not critical for survival. Failure of 
      survival in FcRgamma-/- bone marrow mast cells (BMMCs) was rescued by coculture 
      with IgE-treated wild-type BMMCs, suggesting that survival is induced not 
      directly through FcepsilonRI signals. We found that the survival is predominantly 
      mediated by high production of interleukin 3 (IL-3), evidenced by severe 
      impairment of survival by anti-IL-3 and in IL-3-/- BMMCs. The up-regulation of 
      Bcl-xL/Bcl-2 by IgE was abrogated in IL-3-/- BMMCs, whereas the expression of 
      histidine decarboxylase was normally induced. These results indicate that IL-3 
      plays a crucial role for IgE(-Ag)-induced mast cell survival, functioning in an 
      autocrine manner by inducing the Bcl-xL/Bcl-2 via signal transducer and activator 
      of transduction 5. We further suggest that IgE(-Ag)-mediated gene expression in 
      mast cells is regulated at least 2 mechanisms: autocrine IL-3 dependent and 
      independent.
FAU - Kohno, Masayuki
AU  - Kohno M
AD  - Department of Molecular Genetics, Graduate School of Medicine, Chiba University, 
      Chiba, Japan.
FAU - Yamasaki, Sho
AU  - Yamasaki S
FAU - Tybulewicz, Victor L J
AU  - Tybulewicz VL
FAU - Saito, Takashi
AU  - Saito T
LA  - eng
PT  - Journal Article
DEP - 20041112
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Antigens)
RN  - 0 (Bcl2l1 protein, mouse)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Enzyme Precursors)
RN  - 0 (Interleukin-3)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Milk Proteins)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (Receptors, IgG)
RN  - 0 (STAT5 Transcription Factor)
RN  - 0 (Trans-Activators)
RN  - 0 (bcl-X Protein)
RN  - 37341-29-0 (Immunoglobulin E)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.2 (Syk Kinase)
RN  - EC 2.7.10.2 (Syk protein, mouse)
RN  - EC 2.7.10.2 (lyn protein-tyrosine kinase)
RN  - EC 2.7.10.2 (src-Family Kinases)
SB  - IM
MH  - Animals
MH  - Antigens
MH  - *Autocrine Communication
MH  - Bone Marrow Cells
MH  - *Cell Survival
MH  - DNA-Binding Proteins/metabolism
MH  - Enzyme Precursors/metabolism
MH  - Immunoglobulin E/*physiology
MH  - Interleukin-3/*biosynthesis/physiology
MH  - Intracellular Signaling Peptides and Proteins
MH  - Mast Cells/*cytology/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Milk Proteins/metabolism
MH  - Protein-Tyrosine Kinases/metabolism
MH  - Proto-Oncogene Proteins c-bcl-2/metabolism
MH  - Receptors, IgG/metabolism
MH  - STAT5 Transcription Factor
MH  - Signal Transduction
MH  - Syk Kinase
MH  - Trans-Activators/metabolism
MH  - bcl-X Protein
MH  - src-Family Kinases/metabolism
EDAT- 2004/11/16 09:00
MHDA- 2005/03/25 09:00
CRDT- 2004/11/16 09:00
PHST- 2004/11/16 09:00 [pubmed]
PHST- 2005/03/25 09:00 [medline]
PHST- 2004/11/16 09:00 [entrez]
AID - S0006-4971(20)45817-3 [pii]
AID - 10.1182/blood-2004-07-2639 [doi]
PST - ppublish
SO  - Blood. 2005 Mar 1;105(5):2059-65. doi: 10.1182/blood-2004-07-2639. Epub 2004 Nov 
      12.