Adhesion-dependent interactions between eosinophils and cholinergic nerves.
Eosinophils adhere to airway cholinergic nerves and influence nerve cell function by releasing granule proteins onto inhibitory neuronal M(2) muscarinic receptors. This study investigated the mechanism of eosinophil degranulation by cholinergic nerves. Eosinophils were cocultured with IMR32 cholinergic nerve cells, and eosinophil peroxidase (EPO) or leukotriene C(4) (LTC(4)) release was measured. Coculture of eosinophils with nerves significantly increased EPO and LTC(4) release compared with eosinophils alone. IMR32 cells, like parasympathetic nerves, express the adhesion molecules vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 (ICAM-1). Inhibition of these adhesion molecules alone or in combination significantly inhibited eosinophil degranulation. IMR32 cells also significantly augmented the eosinophil degranulation produced by formyl-Met-Leu-Phe. Eosinophil adhesion to IMR32 cells resulted in an ICAM-1-mediated production of reactive oxygen species via a neuronal NADPH oxidase, inhibition of which significantly inhibited eosinophil degranulation. Additionally, eosinophil adhesion increased the release of ACh from IMR32 cells. These neuroinflammatory cell interactions may be relevant in a variety of inflammatory and neurological conditions.
Kingham
Paul J
PJ
Department of Pharmacology and Therapeutics, University of Liverpool, Liverpool L69 3GE, United Kingdom.
McLean
W Graham
WG
Sawatzky
Deborah A
DA
Walsh
Marie Therese
MT
Costello
Richard W
RW
D000109:Acetylcholine / Q000378:metabolism*; D002448:Cell Adhesion / Q000502:physiology; D002450:Cell Communication / Q000502:physiology*; D015550:Cell Degranulation / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D018920:Coculture Techniques; D047209:Eosinophil Peroxidase; D004804:Eosinophils / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D017997:Leukotriene C4 / Q000378:metabolism; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D010544:Peroxidases / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism / Q000494:pharmacology; D043585:Receptor, Muscarinic M2; D011976:Receptors, Muscarinic / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D017382:Reactive Oxygen Species; D043585:Receptor, Muscarinic M2; D011976:Receptors, Muscarinic; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D017997:Leukotriene C4; D009240:N-Formylmethionine Leucyl-Phenylalanine; D047209:Eosinophil Peroxidase; D010544:Peroxidases; D019255:NADPH Oxidases; D000109:Acetylcholine