Acetylcholine and nicotine stimulate the release of granulocyte-macrophage colony stimulating factor from cultured human bronchial epithelial cells.
Primary cultures of human bronchial epithelial cells (HBE-cells) were established to measure granulocyte-macrophage colony stimulating factor (GM-CSF) release. HBE-cells showed a basal GM-CSF release (82+/-20 ng/well/24 h; 30 donors), which was increased by interleukin-1 beta(IL-1beta, 1 ng/ml) by 270%. This effect was blocked by 1 microM dactinomycin or 10 microM cycloheximide, i.e. the stimulatory effect of IL-1beta depended on de-novo synthesis. Histamine (100 microM) and acetylcholine ( 100 nM) stimulated GM-CSF release more than two-fold above the baseline. Nicotine (1 microM) increased GM-CSF release to a similar extent, and this effect was prevented by 30 microM (+)-tubocurarine. The stimulatory effect was attenuated or even lost with high agonist concentrations (10 microM acetylcholine; 100 microM nicotine) suggesting receptor desensitization. The muscarinic receptor agonist oxotremorine did not affect GM-CSF release. Serotonin, substance P and calcitonin-gene related peptide had no effect on GM-CSF release. In conclusion, acetylcholine can trigger GM-CSF release from human airway epithelial cells via stimulation of nicotinic receptors.
Klapproth
H
H
Department of Pharmacology, University of Mainz, Germany.
Racké
K
K
Wessler
I
I
D000109:Acetylcholine / Q000494:pharmacology*; D001980:Bronchi / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*
D018722:Nicotinic Agonists; D009538:Nicotine; D006632:Histamine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D000109:Acetylcholine