Inhibitory capacity of different steroids on neutrophil migration across a bilayer of endothelial and bronchial epithelial cells.
Neutrophil infiltration to the airway lumen is a common feature of respiratory inflammatory processes. The aim of this study was to evaluate whether different corticosteroids exert any selective effect on the migration of isolated neutrophils. A bilayer of cultured human endothelial and bronchial epithelial cells was used as a model for neutrophil migration through the blood-air barrier. Low spontaneous migration of neutrophils (2.8+/-0.9%, n=8; mean+/-S.E.M.) occurred, while in the absence of any steroid, a migration of 28.5+/-7.6% could be induced by lipopolysaccharide. Pre-incubation during 1 h of epithelial cells with dexamethasone, budesonide, or prednisolone (10(-10)-10(-4) M) showed in all instances a concentration-dependent inhibition following a bell-shaped curve. At 10(-7) M, both dexamethasone and budesonide were on the minimum effect peak of the bell-shaped curve. The peak for prednisolone was found at 10(-8) M. However, when steroid pre-incubation was extended to 4 h, a sigmoid curve was observed, with significant inhibition of migration at concentrations >10(-7) M. Steroids can inhibit neutrophil recruitment through two different pathways with distinct result, depending on the length of incubation time.
van Overveld
Frans J
FJ
Department of Respiratory Medicine, University of Antwerp (UIA), Universiteitsplein 1, B-2610 -Wilrijk, Antwerpen, Belgium. overveld@uia.ua.ac.be
Demkow
Urszula A
UA
Górecka
Dorota
D
Zielinski
Jan
J
De Backer
Wilfried A
WA
D001980:Bronchi / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D020556:Neutrophil Infiltration / Q000187:drug effects* / Q000502:physiology; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D011278:Pregnanes / Q000494:pharmacology; D013256:Steroids / Q000737:chemistry / Q000494:pharmacology*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D007375:Interleukin-1; D008070:Lipopolysaccharides; D011278:Pregnanes; D013256:Steroids; D014409:Tumor Necrosis Factor-alpha