Monomeric IgE stimulates signaling pathways in mast cells that lead to cytokine production and cell survival.
Although IgE binding to mast cells is thought to be a passive presensitization step, we demonstrate herein that monomeric IgE (mIgE) in the absence of antigen (Ag) stimulates multiple phosphorylation events in normal murine bone marrow-derived mast cells (BMMCs). While mIgE does not induce degranulation or leukotriene synthesis, it leads to a more potent production of cytokines than IgE + Ag. Moreover, mIgE prevents the apoptosis of cytokine-deprived BMMCs, likely by maintaining Bcl-X(L) levels and producing autocrine-acting cytokines. The addition of Ag does not increase this IgE-induced survival. Since IgE concentrations as low as 0.1 microg/ml enhance BMMC survival, elevated plasma IgE levels in humans with atopic disorders may contribute to the elevated mast cell numbers seen in these individuals.
Kalesnikoff
J
J
The Terry Fox Laboratory, British Columbia Cancer Agency, 601 West 10th Avenue, Vancouver, British Columbia V5Z 1L3, Canada.
Huber
M
M
Lam
V
V
Damen
J E
JE
Zhang
J
J
Siraganian
R P
RP
Krystal
G
G
D000818:Animals; D017209:Apoptosis / Q000276:immunology; D002470:Cell Survival; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D007073:Immunoglobulin E / Q000276:immunology* / Q000494:pharmacology; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology*; D021962:Membrane Microdomains / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D017455:Receptors, IgE / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*; D048051:p38 Mitogen-Activated Protein Kinases
D016207:Cytokines; D011518:Proto-Oncogene Proteins; D017455:Receptors, IgE; D007073:Immunoglobulin E; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases