Activation of mast cells by immunoglobulin E-receptor cross-linkage, but not through adenosine receptors, induces A1 expression and promotes survival.
BACKGROUND
Mast cells are a potent source of mediators that regulate the inflammatory response in allergy and asthma. Mast cells can be activated through different receptors, for example, via cross-linkage of the high-affinity IgE receptor (Fc epsilon RI) and by adenosine acting on specific receptors. We have recently described mast cell survival of an IgE receptor activation by up-regulation of the anti-apoptotic gene A1.


OBJECTIVE
To compare mast cell survival and expression of A1 after activation through the Fc epsilon RI and by an adenosine agonist.


METHODS
Bone marrow-derived, cultured mouse mast cells (BMCMC) were activated either with IgE+antigen or with the adenosine receptor agonist 5'-N-ethylcarboxamido adenosine (NECA). Release of beta-hexosaminidase, cell viability, phosphorylation of Akt and IkB-alpha, and expression of pro-survival and pro-apoptotic genes were measured after activation.


RESULTS
Activation of BMCMC with NECA caused the release of beta-hexosaminidase, although to a lesser extent than after Fc epsilon RI activation (33% and 98%, respectively). Activation by both NECA and Fc epsilon RI stimulated phosphorylation of Akt (Ser473 and Thr308) and IkB-alpha (Ser32), both of which are implicated in the regulation of cell survival. However, only cells that were activated through Fc epsilon RI, but not by NECA, expressed A1 and exhibited an increased survival rate compared to the control.


CONCLUSIONS
These results show that adenosine receptor activation of BMCMC does not induce the same survival programme in mast cells as does activation through Fc epsilon RI. These findings may be important for understanding the role that mast cells play in asthma provoked by different stimuli.
Möller
C
C
Research Group on Mast Cell Biology, The Rudbeck Laboratory, Department of Genetics and Pathology, Uppsala University, Uppsala, Sweden.
Xiang
Z
Z
Nilsson
G
G
D000241:Adenosine / Q000502:physiology; D019830:Adenosine-5'-(N-ethylcarboxamide) / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D015550:Cell Degranulation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D020672:I-kappa B Proteins / Q000378:metabolism; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D000072000:NF-KappaB Inhibitor alpha; D010766:Phosphorylation / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D058906:Purinergic P1 Receptor Agonists; D017455:Receptors, IgE / Q000378:metabolism*; D018047:Receptors, Purinergic P1 / Q000502:physiology*; D051818:Replication Protein C; D015854:Up-Regulation; D001619:beta-N-Acetylhexosaminidases / Q000378:metabolism
D004268:DNA-Binding Proteins; D020672:I-kappa B Proteins; C000606205:Nfkbia protein, mouse; D011518:Proto-Oncogene Proteins; D058906:Purinergic P1 Receptor Agonists; D017455:Receptors, IgE; D018047:Receptors, Purinergic P1; D000072000:NF-KappaB Inhibitor alpha; D019830:Adenosine-5'-(N-ethylcarboxamide); D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D001619:beta-N-Acetylhexosaminidases; D051818:Replication Protein C; D000241:Adenosine