Modulation of GM-CSF release by enantiomers of β-agonists in human airway smooth muscle

GM-CSF release with enantiomers and propranolol (10 μmol/L; hatched bars) relative to control (dashed line; [enantiomer]=0). (R)-albuterol (n=6), (S)-albuterol (n=4), (R)-+(S)-albuterol (n=4), (R,R)-formoterol (n=6), (S,S)-formoterol (n=4), or (R,R)-+(S,S)-formoterol (n=4). Symbols indicate P < .05 for comparison versus ^∗respective control, ⁺respective enantiomer at same concentration, ^∧respective (R)-enantiomer at same concentration, and ^#(R)-albuterol at same concentration.

A, GM-CSF release by HASMC with propranolol (○) and ICI-118,511 (•). ^∗P < .05 compared with control (0 μmol/L propranolol=467 pg/mL ± 4 pg/mL; 0 μmol/L ICI-118,551=1079 pg/mL ± 28 pg/mL); n=5 experiments per concentration. B, Intracellular cAMP levels in HASMC with propranolol (n=2) and ICI-118,551 (n=4); significance as in A; mean baseline cAMP=1.9 pmol/mL ± 0.1 pmol/mL.

Propranolol concentration and GM-CSF release response relationship versus single concentration (10 μmol/L) of either (R)-albuterol (left) or (R,R)-formoterol (right) in HASMC. Symbols indicate P < .05 for comparison versus^∗ respective control (0 μmol/L propranolol), ^∧(R)-albuterol at same concentration; n=5 experiments/bar.

Intracellular cAMP with increasing (R)-albuterol alone (□; n=2) and with increasing (R)-albuterol plus propranolol (•; 0 μmol/L or 10 μmol/L; n=2), expressed as a function of baseline intracellular cAMP in HASMC with no drugs added (horizontal dashed line; 1.2 pmol/mL ± 0.4 pmol/mL).

GM-CSF release with dibutyryl cAMP alone (•) and with dibutyryl cAMP plus propranolol (○; 100 μmol/L),^∗P < .05; versus 0 μmol/L dibutyryl cAMP, †P < .05; versus dibutyryl cAMP alone at same concentration; r²>.99 for regression of both data sets; horizontal dashed line indicates control GM-CSF release with 0 μmol/L dibutyryl cAMP (1672 pg/mL ± 22 pg/mL); n=5 experiments per set.

Effects of dexamethasone (Dex) in combination with enantiomers. GM-CSF expressed as ratios relative to –Dex, 0 enantiomer control (range: 1800-2700 pg/mL); percentage change values as shown. ^∗P < .05 vs –Dex, 0 agonist (no drugs) control; ⁺P < .05 vs –Dex, 10 μmol/L agonist; ^∧P < .05 vs +Dex, 0 agonist; n=4-10 experiments/bar.