ISSN:
1365-3083
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
It is well known that the exposure of endothelial cells to IL-1β induces an increase in endothelial cell adhesiveness for leucocytes. Using rat heart endothelial cells we found that exposure of endothelial cells to IL-1β (100U/ml) induces a 133-fold increase in the intracellular concentration of cyclic-GMP; from 11.5×0.2fm to 1530 × 117.8 fm (per 106 cells). Therefore, we examined whether cyclie-GMP is involved in the regulation of endothelial adhesiveness for leucocytes. Cyclic-GMP analogue, dibutyryl cyclic-GMP (0.01–0.05mm), similarly to IL-1β, increased endothelial cell adhesiveness for leucocytes. Methylene blue, an inhibitor of guanylate cyclase, and KT5823, a specific inhibitor of cyclic-GMP-dependent protein kinase, inhibited both basal as well as IL-1β-induced endothelial cell adhesiveness for leucocytes, and KT5823 abolished the dibutyryl-cyclic-GMP-induced increase in endothelial adhesive ness. The effect of cyclic-GMP, induced by IL-1β treatment, on the endothelial adhesiveness may be either direct or indirect because of the time-gap between the rise in cyclic-GMP level and the increase of endothelial adhesiveness.IL-1β (100 U/ml) and dibuthyryl-cyclic-GMP (0.01 mm) both induced an increase in the expression of intercellular adhesion molecule-1 by endothelial cells. However, the fact that KT5823 failed to prevent this increase, suggests that, although the IL-lγb-induced increase in adhesiveness is caused by the increase in intracellular levels of cyclic-GMP, it may not be mediated through intercellular adhesion molecule-1.In conclusion, the results obtained indicate that endothelial cell adhesiveness for leucocytes is, in part, regulated by the cyclic-GMP-dependent signal transduction pathway.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1111/j.1365-3083.1994.tb03412.x
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