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Inhibition of neutrophil adhesion by adenosine and an adenosine kinase inhibitor. The role of selectins.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 1995 Jan 01; Vol. 154 (1), pp. 326-34. - Publication Year :
- 1995
-
Abstract
- Adenosine and adenosine analogues exhibit anti-inflammatory effects in vitro and in vivo, but their usefulness is limited by profound cardiovascular side effects. Therefore, we synthesized inhibitors of an enzyme involved in adenosine metabolism, adenosine kinase (AK) (EC 2.7.1.20), to enhance endogenous adenosine concentrations at sites of inflammation. GP-1-515 (4-amino-1-(5-amino-5-deoxy-1-beta-D- ribofuranosyl)-3-bromo-pyrazolo[3,4-d]pyrimidine), a novel AK inhibitor, decreased adhesion of activated human neutrophils to cultured endothelial cell monolayers by increasing local adenosine levels. The mechanism of inhibition in this assay seemed to involve selectin blockade and was independent of the beta 2 integrins. GP-1-515 and 2-chloroadenosine (a nonmetabolizable adenosine analogue) had no effect on the surface expression or shedding of adhesion molecules. An agent that disrupts the cytoskeleton, cytochalasin B, mimicked the effect of adenosine on cell adhesion. Interactions between L-selectin and the neutrophil cytoskeleton might be altered by adenosine and could contribute to adenosine-mediated adhesion inhibition.
- Subjects :
- 2-Chloroadenosine pharmacology
Adenosine metabolism
CD18 Antigens physiology
Cell Adhesion drug effects
Cell Adhesion Molecules physiology
Cells, Cultured
Cytoskeleton physiology
Cytoskeleton ultrastructure
Depression, Chemical
E-Selectin
Endothelium, Vascular cytology
Endothelium, Vascular drug effects
Endothelium, Vascular metabolism
Humans
Interleukin-1 pharmacology
L-Selectin
N-Formylmethionine Leucyl-Phenylalanine pharmacology
Neutrophils metabolism
Neutrophils ultrastructure
Adenosine pharmacology
Adenosine Kinase antagonists & inhibitors
Neutrophils drug effects
Ribonucleosides pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 0022-1767
- Volume :
- 154
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 7527814