PMID- 9224965
OWN - NLM
STAT- MEDLINE
DCOM- 19970807
LR  - 20190826
IS  - 0161-5890 (Print)
IS  - 0161-5890 (Linking)
VI  - 34
IP  - 3
DP  - 1997 Feb
TI  - Anti-ganglioside monoclonal antibody AA4 selectively inhibits IgE-induced signal 
      transduction pathways in rat basophilic leukemia cells.
PG  - 227-35
AB  - In rat basophilic leukemia 2H3 (RBL-2H3) cells, mAb AA4 binds to two derivatives 
      of ganglioside GD1b that associate with the Src family kinase p53/56lyn and a 
      serine kinase. Pre-incubation of cells with mAb AA4 blocks immunoglobulin E (IgE) 
      mediated histamine release. In the present study we investigated the effect of 
      incubation with mAb AA4 on signal transduction events. In addition to stimulation 
      of the high affinity IgE receptor (Fc epsilonRI), cells were also activated by 
      the calcium ionophore A23187 and the acetylcholine agonist carbachol in RBL-2H3 
      cells transfected with the G protein-coupled m3 muscarinic receptor. Incubation 
      of cells with mAb AA4 in a dose-dependent manner inhibited the following Fc 
      epsilonRI-induced signal transduction events: the increase of intracellular free 
      calcium, phosphoinositol breakdown, tyrosine phosphorylation of proteins 
      including the beta- of Fc epsilonRI and secretion. However, there was no 
      inhibition of degranulation or of these biochemical events when cells were 
      stimulated with calcium ionophore or activated via a G protein-coupled pathway. 
      Our results demonstrate that mAb AA4 selectively blocks Fc epsilonRI-induced cell 
      activation at a very early step upstream of receptor tyrosine phosphorylation. As 
      mAb AA4 has previously been found to bind to gangliosides associated with Fc 
      epsilonRI, inhibition of very early biochemical events may be due to interaction 
      of mAb AA4 with the Fc epsilonRI induced signal transduction cascade at the 
      receptor level.
FAU - Stephan, V
AU  - Stephan V
AD  - University Children's Hospital, Dusseldorf, Germany.
FAU - Seibt, A
AU  - Seibt A
FAU - Dukanovic, D
AU  - Dukanovic D
FAU - Skasa, M
AU  - Skasa M
FAU - Swaim, W D
AU  - Swaim WD
FAU - Berenstein, E H
AU  - Berenstein EH
FAU - Siraganian, R P
AU  - Siraganian RP
FAU - Wahn, V
AU  - Wahn V
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Mol Immunol
JT  - Molecular immunology
JID - 7905289
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Gangliosides)
RN  - 0 (Phosphatidylinositols)
RN  - 0 (Phosphoproteins)
RN  - 0 (Receptors, IgE)
RN  - 21820-51-9 (Phosphotyrosine)
RN  - 333DO1RDJY (Serotonin)
RN  - 37341-29-0 (Immunoglobulin E)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Antibodies, Monoclonal
MH  - Calcium/metabolism
MH  - Cytoplasm/metabolism
MH  - Gangliosides/*physiology
MH  - Immunoglobulin E/*immunology
MH  - Mast Cells/*physiology
MH  - Phosphatidylinositols/metabolism
MH  - Phosphoproteins/metabolism
MH  - Phosphorylation
MH  - Phosphotyrosine/metabolism
MH  - Rats
MH  - Receptors, IgE/*physiology
MH  - Serotonin/metabolism
MH  - Signal Transduction
MH  - Tumor Cells, Cultured
EDAT- 1997/02/01 00:00
MHDA- 1997/02/01 00:01
CRDT- 1997/02/01 00:00
PHST- 1997/02/01 00:00 [pubmed]
PHST- 1997/02/01 00:01 [medline]
PHST- 1997/02/01 00:00 [entrez]
AID - S0161589097000266 [pii]
AID - 10.1016/s0161-5890(97)00026-6 [doi]
PST - ppublish
SO  - Mol Immunol. 1997 Feb;34(3):227-35. doi: 10.1016/s0161-5890(97)00026-6.