The effect of nedocromil sodium on human airway epithelial cell-induced eosinophil chemotaxis and adherence to human endothelial cell in vitro.
Although some studies have shown that long-term treatment of asthmatics with nedocromil sodium can reduce airway hyperresponsiveness and improve symptoms and lung function, the mechanisms underlying its effects are not well understood. We have investigated the effect of nedocromil sodium on eosinophil chemotaxis, eosinophil adherence to human endothelial cells and release of soluble intercellular adhesion molecule-1 (sICAM-1) from endothelial cells, induced by conditioned medium collected from cultured human bronchial epithelial cells. Conditioned medium significantly increased eosinophil chemotaxis from a baseline median value of 2.1 (range 1.9-4.5) cells-high power field(-1) (HPF) to 10.5 (range 7.8-12.3) cells-HPF(-1) (p<0.05). Similarly, conditioned medium significantly increased eosinophil adherence to endothelial cells from a baseline value of 9 (range 8-12)% to 23 (range 21-30)% (p<0.05). Nedocromil sodium, at 10(-5) M concentration, significantly attenuated the eosinophil chemotaxis and adherence induced by conditioned medium. Conditioned medium also significantly increased the release of sICAM-1 from endothelial cells, from a baseline value of 11.5 (range 8.1-15.4) pg x microg(-1) protein to 67.6 (range 55.6-73.5) pg x microg(-1) protein (p<0.05). This was significantly attenuated by anti-tumour necrosis factor-alpha (TNF-alpha), anti-interleukin-1beta (IL-1beta) and 10(-5) M nedocromil sodium. These findings suggest that human bronchial epithelial cell-derived mediators may potentiate eosinophil activity, and that this can be modulated by nedocromil sodium, suggesting a possible mechanism underlying its anti-inflammatory effect.
Abdelaziz
M M
MM
Academic Dept of Respiratory Medicine, St Bartholomew's and the Royal London School of Medicine and Dentistry, The London Chest Hospital, UK.
Devalia
J L
JL
Khair
O A
OA
Rusznak
C
C
Calderon
M
M
Sapsford
R J
RJ
Bayram
H
H
Davies
R J
RJ
D018927:Anti-Asthmatic Agents / Q000494:pharmacology*; D001980:Bronchi / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004727:Endothelium / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004804:Eosinophils / Q000187:drug effects* / Q000378:metabolism; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000187:drug effects* / Q000378:metabolism; D017835:Nedocromil / Q000494:pharmacology*
D018927:Anti-Asthmatic Agents; D017835:Nedocromil; D018799:Intercellular Adhesion Molecule-1