Angiopeptin, the octapeptide analogue of somatostatin, decreases rat heart endothelial cell adhesiveness for mononuclear cells.
The effect of angiopeptin, a stable analogue of somatostatin, was studied on basal and interleukin-1-beta-induced endothelial cell adhesiveness for mononuclear cells, and compared to the effect of somatostatin. Angiopeptin and somatostatin decreased basal and interleukin-1-beta-induced endothelial cell adhesiveness for mononuclear cells. The decreased mononuclear cells adhesion to endothelial cells exposed to angiopeptin and somatostatin is not due to modulation of the expression of intrecellular adhesion molecule-1 because neither angiopeptin nor somatostatin decreased basal and interleukin-1-beta-induced expression of this adhesion molecule. The effect of angiopeptin in inhibiting endothelial cell adhesiveness for mononuclear cells was abolished by addition of dibutyryl-cyclic AMP. Angiopeptin induced a transient decrease in basal and interleukin-1-beta-induced cyclic AMP levels in endothelial cells. Exposure of unstimulated and interleukin-1-beta-activated endothelial cells to KT5720, a specific inhibitor of cyclic AMP-dependent protein kinase, decreased endothelial cell adhesiveness for mononuclear cells. Thus, angiopeptin most likely diminishes endothelial adhesiveness for mononuclear cells by affecting the cyclic AMP-dependent protein kinase signal transduction pathway. The findings suggest that angiopeptin and somatostatin may modify the development of the immune response by attenuating endothelial cell adhesiveness for mononuclear cells. Angiopeptin may have a potential clinical application as a modulator of some aspects of the immune response due to its long half-life and prolonged inhibitory effect on interleukin-1-beta induced endothelial adhesiveness for mononuclear cells.
Leszczynski
D
D
Department of Surgery, Georgetown University Medical Center, Washington, DC.
Josephs
M D
MD
Fournier
R S
RS
Foegh
M L
ML
D000595:Amino Acid Sequence; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002227:Carbazoles; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D005434:Flow Cytometry; D006321:Heart / Q000187:drug effects; D007211:Indoles / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects*; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000494:pharmacology*; D010456:Peptides, Cyclic; D047428:Protein Kinase Inhibitors; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000494:pharmacology
D002227:Carbazoles; D007211:Indoles; D009842:Oligopeptides; D010456:Peptides, Cyclic; D047428:Protein Kinase Inhibitors; D011758:Pyrroles; C060347:lanreotide; D013004:Somatostatin; C057416:KT 5720; D003994:Bucladesine