Eosinophil adhesion to cholinergic IMR-32 cells protects against induced neuronal apoptosis.
Eosinophils release a number of mediators that are potentially toxic to nerve cells. However, in a number of inflammatory conditions, such as asthma and inflammatory bowel disease, it has been shown that eosinophils localize to nerves, and this is associated with enhanced nerve activity. In in vitro studies, we have shown that eosinophil adhesion via neuronal ICAM-1 leads to activation of neuronal NF-kappaB via an ERK1/2-dependent pathway. In this study, we tested the hypothesis that eosinophil adhesion to nerves promotes neural survival by protection from inflammation-associated apoptosis. Exposure of differentiated IMR-32 cholinergic nerve cells to IL-1beta, TNF-alpha, and IFN-gamma, or culture in serum-deprived medium, induced neuronal apoptosis, as detected by annexin V staining, caspase-3 activation, and DNA laddering. Addition of human eosinophils to IMR-32 nerve cells completely prevented all these features of apoptosis. The mechanism of protection by eosinophils was by an adhesion-dependent activation of ERK1/2, which led to the induced expression of the antiapoptotic gene bfl-1. Adhesion to nerve cells did not influence the expression of the related genes bax and bad. Thus, prevention of apoptosis by eosinophils may be a mechanism by which these cells regulate neural plasticity in the peripheral nervous system.
Morgan
Ross K
RK
Department of Medicine, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin 9, Ireland.
Kingham
Paul J
PJ
Walsh
Marie Therese
MT
Curran
David R
DR
Curran
David C
DC
Durcan
Niamh
N
McLean
W Graham
WG
Costello
Richard W
RW
D017209:Apoptosis / Q000502:physiology*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002448:Cell Adhesion / Q000502:physiology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D018920:Coculture Techniques; D053938:DNA Fragmentation; D004789:Enzyme Activation / Q000502:physiology; D004804:Eosinophils / Q000502:physiology*; D006801:Humans; D015778:Minor Histocompatibility Antigens; D019950:Mitogen-Activated Protein Kinase 1 / Q000502:physiology; D048052:Mitogen-Activated Protein Kinase 3 / Q000502:physiology; D009447:Neuroblastoma / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000201:enzymology / Q000378:metabolism / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D015398:Signal Transduction / Q000502:physiology
C096816:BCL2-related protein A1; D015778:Minor Histocompatibility Antigens; D019253:Proto-Oncogene Proteins c-bcl-2; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases