Inhibition of neutrophil migration and oxygen free radical release by metipranolol and timolol.
Propanolol and metoprolol exert adrenoceptor-independent effects including scavenging of free radicals and inhibition of protein kinase C leading to inhibition of leukocyte migration and radical release as a consequence. Whether topically used metipranolol and timolol exert such effects is unknown. Neutrophil chemotaxis was tested using modified Boyden microchemotaxis chambers. Respiratory burst activity of neutrophils was detected fluorometrically. Radical scavenging properties were tested using 2',7'-dichlorofluorescein diacetate. Metipranolol and timolol inhibited neutrophil chemotaxis at doses in the micromolar range, oxygen free radical production triggered with formyl-Met-Leu-Phe was inhibited at higher concentration. Protein kinase C involvement, suggested to trigger free radical production with phorbol myristate acetate, was antagonized. A direct radical scavenging effect of the beta-blockers was also seen. Inhibition of neutrophil chemotaxis and free radical production is a novel mode of action of metipranolol and timolol that may be relevant for beneficial effects in the topical treatment of eye disease.
Djanani
Angela
A
Laboratory of Intensive Care Medicine, Division of General Internal Medicine, Department of Medicine, University of Innsbruck, Innsbruck, Austria.
Kaneider
Nicole C
NC
Meierhofer
Christian
C
Sturn
Daniel
D
Dunzendorfer
Stefan
S
Allmeier
Helmut
H
Wiedermann
Christian J
CJ
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000187:drug effects* / Q000502:physiology; D016166:Free Radical Scavengers / Q000494:pharmacology; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D014290:Metipranolol / Q000494:pharmacology*; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology; D010100:Oxygen / Q000378:metabolism*; D016897:Respiratory Burst / Q000187:drug effects; D013999:Timolol / Q000494:pharmacology*
D000319:Adrenergic beta-Antagonists; D016166:Free Radical Scavengers; D005609:Free Radicals; D013999:Timolol; D010100:Oxygen; D014290:Metipranolol