FcepsilonRI aggregation promotes survival of connective tissue-like mast cells but not mucosal-like mast cells.
Mast cells play a critical role in IgE-dependent immediate hypersensitivity reactions. This is facilitated by their capacity to release inflammatory mediators and to undergo activation-induced survival upon cross-linking of the high-affinity IgE-receptor (FcepsilonRI). Due to their heterogeneity, mast cells can be divided into two major groups: the connective tissue mast cells and the mucosal mast cells. We have previously shown that IL-3-dependent bone marrow-derived mast cells can undergo activation-induced survival that is dependent on the prosurvival gene A1. In this study, we have used two different protocols to develop murine connective tissue-like mast cells (CTLMC) and mucosal-like mast cells (MLMC) to investigate their capacity to survive an allergic reaction in vitro. In this study, we demonstrate that FcepsilonRI stimulation promotes survival of CTLMC but not MLMC. Similarly, a prominent induction of A1 is observed only in CTLMC but not MLMC. MLMC have a higher basal level of the proapoptotic protein Bim compared with CTLMC. These findings demonstrate a difference among mast cell populations in their ability to undergo activation-induced survival after FcepsilonRI stimulation, which might explain the slower turnover of CTMC in IgE-dependent reactions.
Ekoff
Maria
M
Department of Medicine, Clinical Immunology and Allergy Unit, Karolinska Institutet, KS L2:04 Stockholm, Sweden.
Strasser
Andreas
A
Nilsson
Gunnar
G
D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D000072224:Bcl-2-Like Protein 11; D002470:Cell Survival; D003239:Connective Tissue Cells / Q000166:cytology / Q000276:immunology*; D008407:Mast Cells / Q000166:cytology / Q000276:immunology*; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D008817:Mice, Mutant Strains; D015778:Minor Histocompatibility Antigens; D009092:Mucous Membrane / Q000276:immunology; D011518:Proto-Oncogene Proteins / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D017455:Receptors, IgE / Q000819:agonists / Q000276:immunology*; D015854:Up-Regulation
D051017:Apoptosis Regulatory Proteins; C096816:BCL2-related protein A1; D000072224:Bcl-2-Like Protein 11; C000606776:Bcl2l11 protein, mouse; D008565:Membrane Proteins; D015778:Minor Histocompatibility Antigens; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D017455:Receptors, IgE