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 facto r (GM-CSF) release. HBE-cells showed a basal GM-CSF release (82+/-20 n g/well/24 h; 30 donors), which was increased by interleukin-1 beta (IL -1 beta, 1 ng/ml) by 270%. This effect was blocked by 1 mu M dactinomy cin or 10 mu M cycloheximide, i.e. the stimulatory effect of IL-1 beta depended on de-novo synthesis. Histamine (100 mu M) and acetylcholine (100 nM) stimulated GM-CSF release more than two-fold above the basel ine. Nicotine (1 mu M) increased GM-CSF release to a similar extent, a nd this effect was prevented by 30 mu M (+)-tubocurarine. The stimulat ory effect was attenuated or even lost with high agonist concentration s (10 mu M acetylcholine; 100 mu M nicotine) suggesting receptor desen sitization. The muscarinic receptor agonist oxotremorine did not affec t GM-CSF release. Serotonin, substance P and calcitonin-gene related p eptide had no effect on GM-CSF release. In conclusion, acetylcholine c an trigger GM-CSF release from human airway epithelial cells via stimu lation of nicotinic receptors.