Acetylcholine stimulates bronchial epithelial cells to release neutrophil and monocyte chemotactic activity.
Bronchial asthma is accompanied by inflammatory cell infiltration in the airway. Increased bronchial reactivity to cholinergic stimulation is well recognized in patients with bronchial asthma. Thus, we postulated that acetylcholine (ACh) stimulates bronchial epithelial cells (BEC) to release neutrophil and monocyte chemotactic activity (NCA and MCA). To test this hypothesis, bovine BEC monolayers were tested for NCA and MCA by a blind-well chemotactic chamber technique. BEC released NCA and MCA in response to ACh in a dose-dependent and time-dependent manner. Molecular sieve column chromatography revealed that ACh induced a single low-molecular-weight peak (near 400) for NCA and two low-molecular-weight peaks (near 12,000 and 400) for MCA. The release of NCA and MCA was inhibited by the lipoxygenase inhibitors, nordihydroguaiaretic acid and diethylcarbamazine. Cigarette smoke is a well-recognized stimulus for airway inflammation. To determine whether smoke might activate BEC to release NCA by stimulating nicotinic ACh receptors, we further characterized the ACh receptors, using nicotine and nicotinic and muscarinic receptor antagonists. Nicotine, the nicotinic receptor antagonist d-tubocurarine, and the M2 receptor antagonist gallamine did not modulate the release of NCA in response to ACh. In contrast, atropine and the M1 receptor antagonist, pirenzepine, inhibited the release of NCA. These data demonstrate that ACh stimulates BEC to release lipoxygenase-derived NCA and MCA through the muscarinic receptor.
Koyama
S
S
Research Service, Omaha Veterans Affairs Medical Center, Nebraska.
Rennard
S I
SI
Robbins
R A
RA
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D001980:Bronchi / Q000166:cytology / Q000378:metabolism*; D002630:Chemotactic Factors / Q000378:metabolism*; D004847:Epithelial Cells; D004848:Epithelium / Q000378:metabolism; D009000:Monocytes / Q000378:metabolism*; D009504:Neutrophils / Q000378:metabolism*; D011950:Receptors, Cholinergic / Q000502:physiology
D002630:Chemotactic Factors; D011950:Receptors, Cholinergic; D000109:Acetylcholine