Eosinophil adhesion to cholinergic nerves via ICAM-1 and VCAM-1 and associated eosinophil degranulation.
In vivo, eosinophils localize to airway cholinergic nerves in antigen-challenged animals, and inhibition of this localization prevents antigen-induced hyperreactivity. In this study, the mechanism of eosinophil localization to nerves was investigated by examining adhesion molecule expression by cholinergic nerves. Immunohistochemical and functional studies demonstrated that primary cultures of parasympathetic nerves express vascular cell adhesion molecule-1 (VCAM-1) and after cytokine pretreatment with tumor necrosis factor-alpha and interferon-gamma intercellular adhesion molecule-1 (ICAM-1). Eosinophils adhere to these parasympathetic neurones after cytokine pretreatment via a CD11/18-dependent pathway. Immunohistochemistry and Western blotting showed that a human cholinergic nerve cell line (IMR-32) expressed VCAM-1 and ICAM-1. Inhibitory experiments using monoclonal blocking antibodies to ICAM-1, VCAM-1, or CD11/18 and with the very late antigen-4 peptide inhibitor ZD-7349 showed that eosinophils adhered to IMR-32 cells via these adhesion molecules. The protein kinase C signaling pathway is involved in this process as a specific inhibitor-attenuated adhesion. Eosinophil adhesion to IMR-32 cells was associated with the release of eosinophil peroxidase and leukotriene C(4). Thus eosinophils adhere to cholinergic nerves via specific adhesion molecules, and this leads to eosinophil activation and degranulation; this may be part of the mechanism of eosinophil-induced vagal hyperreactivity.
Sawatzky
Deborah A
DA
Department of Pharmacology and Therapeutics, University of Liverpool, Liverpool L69 3GE, United Kingdom.
Kingham
Paul J
PJ
Court
Emma
E
Kumaravel
Bharathy
B
Fryer
Allison D
AD
Jacoby
David B
DB
McLean
W Graham
WG
Costello
Richard W
RW
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D015550:Cell Degranulation / Q000502:physiology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004804:Eosinophils / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D005260:Female; D006168:Guinea Pigs; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D039041:Integrin alpha4beta1; D016023:Integrins / Q000037:antagonists & inhibitors; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis*; D017997:Leukotriene C4 / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D010275:Parasympathetic Nervous System / Q000166:cytology / Q000378:metabolism; D010456:Peptides, Cyclic / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D016201:Receptors, Lymphocyte Homing / Q000037:antagonists & inhibitors; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis*
D000911:Antibodies, Monoclonal; D004791:Enzyme Inhibitors; D039041:Integrin alpha4beta1; D016023:Integrins; D010456:Peptides, Cyclic; D016201:Receptors, Lymphocyte Homing; D019010:Vascular Cell Adhesion Molecule-1; C418806:ZD7349; D018799:Intercellular Adhesion Molecule-1; D017997:Leukotriene C4; D006493:Heparin; D011493:Protein Kinase C; D000109:Acetylcholine