Effects of eosinophils on nerve cell morphology and development: the role of reactive oxygen species and p38 MAP kinase.
The adhesion of eosinophils to nerve cells and the subsequent release of eosinophil products may contribute to the pathogenesis of conditions such as asthma and inflammatory bowel disease. In this study we have separately examined the consequences of eosinophil adhesion and degranulation for nerve cell morphology and development. Eosinophils induced neurite retraction of cultured guinea pig parasympathetic nerves and differentiated IMR32 cholinergic neuroblastoma cells. Inhibition of eosinophil adhesion to IMR32 cells attenuated this retraction. Eosinophil adhesion to IMR32 cells led to tyrosine phosphorylation of a number of nerve cell proteins, activation of p38 MAP kinase, and generation of neuronal reactive oxygen species (ROS). Inhibition of tyrosine kinases with genistein prevented both the generation of ROS in the nerve cells and neurite retraction. The p38 MAP kinase inhibitor SB-239063 prevented neurite retraction but had no effect on the induction of ROS. Thus eosinophils induced neurite retraction via two distinct pathways: by generation of tyrosine kinase-dependent ROS and by p38 MAP kinase. Eosinophils also prevented neurite outgrowth during differentiation of IMR32 cells. In contrast to their effect on neurite retraction, this effect was mimicked by medium containing products released from eosinophils and by eosinophil major basic protein. These results indicate that eosinophils modify the morphology of nerve cells by distinct mechanisms that involve adhesion and released proteins.
Kingham
Paul J
PJ
Dept. of Pharmacology and Therapeutics, Univ. of Liverpool, The Sherrington Bldgs., Ashton St., Liverpool L69 3GE, UK.
McLean
W Graham
WG
Walsh
Marie-Therese
MT
Fryer
Allison D
AD
Gleich
Gerald J
GJ
Costello
Richard W
RW
D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D015550:Cell Degranulation / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D016922:Cellular Senescence / Q000502:physiology; D004789:Enzyme Activation; D004804:Eosinophils / Q000378:metabolism / Q000502:physiology*; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000494:pharmacology*; D004676:Myelin Basic Protein / Q000494:pharmacology; D016501:Neurites / Q000187:drug effects / Q000502:physiology; D009447:Neuroblastoma / Q000473:pathology / Q000503:physiopathology; D009474:Neurons / Q000166:cytology* / Q000473:pathology / Q000502:physiology*; D010275:Parasympathetic Nervous System / Q000166:cytology / Q000502:physiology; D011107:Polylysine / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014132:Trachea / Q000294:innervation; D048051:p38 Mitogen-Activated Protein Kinases
D004676:Myelin Basic Protein; D017382:Reactive Oxygen Species; D011107:Polylysine; D011505:Protein-Tyrosine Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases