alpha3alpha5beta2-Nicotinic acetylcholine receptor contributes to the wound repair of the respiratory epithelium by modulating intracellular calcium in migrating cells.
Nicotinic acetylcholine receptors (nAChRs), present in human bronchial epithelial cells (HBECs), have been shown in vitro to modulate cell shape. Because cell spreading and migration are important mechanisms involved in the repair of the bronchial epithelium, we investigated the potential role of nAChRs in the wound repair of the bronchial epithelium. In vivo and in vitro, alpha3alpha5beta2-nAChRs accumulated in migrating HBECs involved in repairing a wound, whereas alpha7-nAChRs were predominantly observed in stationary confluent cells. Wound repair was improved in the presence of nAChR agonists, nicotine, and acetylcholine, and delayed in the presence of alpha3beta2 neuronal nAChR antagonists, mecamylamine, alpha-conotoxin MII, and kappa-bungarotoxin; alpha-bungarotoxin, an antagonist of alpha7-nAChR, had no effect. Addition of nicotine to a repairing wound resulted in a dose-dependent transient increase of intracellular calcium in migrating cells that line the wound edge. Mecamylamine and kappa-bungarotoxin inhibited both the cell-migration speed and the nicotine-induced intracellular calcium increase in wound-repairing migrating cells in vitro. On the contrary alpha-bungarotoxin had no significant effect on migrating cells. These results suggest that alpha3alpha5beta2-nAChRs actively contribute to the wound repair process of the respiratory epithelium by modulating intracellular calcium in wound-repairing migrating cells.
Tournier
Jean-Marie
JM
INSERM UMRS-514, 45 rue Cognacq-Jay, 51092 Reims Cedex, France. jm.tournier@univ-reims.fr
Maouche
Kamel
K
Coraux
Christelle
C
Zahm
Jean-Marie
JM
Cloëz-Tayarani
Isabelle
I
Nawrocki-Raby
Béatrice
B
Bonnomet
Arnaud
A
Burlet
Henriette
H
Lebargy
François
F
Polette
Myriam
M
Birembaut
Philippe
P
D000368:Aged; D000369:Aged, 80 and over; D002118:Calcium / Q000378:metabolism*; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D007424:Intracellular Fluid / Q000737:chemistry; D008875:Middle Aged; D009538:Nicotine / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000378:metabolism*; D020545:Respiratory Mucosa / Q000187:drug effects / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014945:Wound Healing / Q000187:drug effects / Q000502:physiology*
D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D009538:Nicotine; D002118:Calcium