Premium
IL‐1β‐Stimulated Leucocyte–Endothelial Adhesion is Regulated, in Part, by the Cyclic‐GMP‐Dependent Signal Transduction Pathway
Author(s) -
LESZCZYNSKI D.,
JOSEPHS M. D.,
FOEGH M. L.
Publication year - 1994
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1111/j.1365-3083.1994.tb03412.x
Subject(s) - intracellular , endothelial stem cell , adhesion , signal transduction , chemistry , microbiology and biotechnology , intercellular adhesion molecule 1 , cell adhesion , medicine , endocrinology , biology , cell , biochemistry , in vitro , organic chemistry
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 11.5×0.2f m to 1530 × 117.8 f m (per 10 6 cells). Therefore, we examined whether cyclie‐GMP is involved in the regulation of endothelial adhesiveness for leucocytes. Cyclic‐GMP analogue, dibutyryl cyclic‐GMP (0.01–0.05m m ), 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 m m ) 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.