Angiopeptin, a somatostatin-14 analogue, decreases adhesiveness of rat leukocytes to unstimulated and IL-1 beta-activated rat heart endothelial cells.
We have previously demonstrated that somatostatin-14 and its octapeptide analogue, angiopeptin, decrease the ability of rat heart endothelial cells to bind leukocytes [Leszczynski, et al., Reg. Pept. 43 (1993) 131-140]. Here, we examined whether exposure of leukocytes to angiopeptin modifies their adhesiveness to the unstimulated and to IL-1 beta-activated endothelium. Monolayers of unstimulated endothelial cells bind 274 +/- 12 leukocytes/mm2. Exposure of leukocytes for 1, 4 and 24 hours to angiopeptin (1 microM) reduced significantly (p < 0.05) adhesion of leukocytes from 274 +/- 12 to 188 +/- 10, 185 +/- 8 and 172 +/- 3 cells/mm2, respectively. Stimulation of endothelial cells with Il-1 beta (100 U/ml) for 24 hours increased endothelial adhesiveness from 274 +/- 12 to 381 +/- 17 adhering leukocytes/mm2. Exposure of leukocytes for 1, 4 and 24 hours to angiopeptin (1 microM) reduced significantly (p < 0.05) binding of leukocytes to IL-1 beta-activated endothelium from 381 +/- 17 to 237 +/- 8, 254 +/- 11 and 248 +/- 13 cells/mm2, respectively. Angiopeptin had no effect on the expression of lymphocyte function-associated molecule-1 (LFA-1; CD11a/CD18) by leukocytes, as assessed by flow cytometry. This suggests that angiopeptin modulates adhesive properties of leukocytes by (1) altering the expression of other than LFA-1 adhesion molecule(s) and/or (2) modulating the affinity of adhesion molecule(s) expressed by leukocytes. In conclusion, our results demonstrate that angiopeptin reduces leukocyte adhesiveness to unstimulated and to IL-1 beta-activated endothelium. It suggests that angiopeptin may suppress immune response via modulation of the leukocyte-endothelial interaction.
Leszczynski
D
D
Department of Research, Finnish Centre for Radiation and Nuclear Safety, Helsinki.
Dunsky
K
K
Josephs
M D
MD
Zhao
Y
Y
Foegh
M L
ML
D000818:Animals; D002317:Cardiovascular Agents / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004727:Endothelium / Q000187:drug effects; D006321:Heart / Q000187:drug effects*; D007375:Interleukin-1 / Q000494:pharmacology*; D007962:Leukocytes / Q000187:drug effects*; D009842:Oligopeptides / Q000494:pharmacology*; D010456:Peptides, Cyclic; D051381:Rats; D011919:Rats, Inbred Strains; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000494:pharmacology; D013997:Time Factors
D002317:Cardiovascular Agents; D007375:Interleukin-1; D009842:Oligopeptides; D010456:Peptides, Cyclic; C060347:lanreotide; D013004:Somatostatin