Angiopeptin, a somatostatin-14 analogue, decreases adhesiveness of rat Leukocytes to unstimulated and IL-1β-activated rat heart endothelial cells

• Published in: Life sciences (1973) Vol. 57; no. 15; pp. PL217 - PL223
• Main Authors: Leszczynski, Dariusz, Dunsky, Kevin, Josephs, Michael D., Zhao, Yejun, Foegh, Marie L.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01.09.1995
• Subjects: angiopeptin; Animals; BIM 23014c; Cardiovascular Agents - pharmacology; Cell Adhesion - drug effects; Dose-Response Relationship, Drug; Endothelium - drug effects; Heart - drug effects; Interleukin-1 - pharmacology; leukocyte-endothelial interaction; Leukocytes - drug effects; Oligopeptides - pharmacology; Rats; Rats, Inbred Strains; Somatostatin - analogs & derivatives; Somatostatin - pharmacology; somatostatin-14; Time Factors; somatostatin-14; leukocyte-endothelial interaction; angiopeptin; BIM 23014c
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/0024-3205(95)02112-V

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-1β-activated endothelium. Monolayers of unstimulated endothelial cells bind 274 ± 12 leukocytes/mm 2. Exposure of leukocytes for 1, 4 and 24 hours to angiopeptin (1 μM) reduced significantly (p < 0.05) adhesion of leukocytes from 274 ± 12 to 188 ± 10, 185 ± 8 and 172 ± 3 cells/mm 2, respectively. Stimulation of endothelial cells with IL-1β (100U/ml) for 24 hours increased endothelial adhesiveness from 274 +- 12 to 381 ± 17 adhering leukocytes/mm 2. Exposure of leukocytes for 1, 4 and 24 hours to angiopeptin (1μM) reduced significantly (p < 0.05) binding of leukocytes to IL-1β-activated endothelium from 381 ± 17 to 237 ± 8, 254 ± 11 and 248 ± 13 cells/mm 2, respectively. Angiopeptin had no effect on the expression of lymphocyte function-associated molecule-1 (LFA-1; CDlla/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-1β-activated endothelium. It suggests that angiopeptin may suppress immune response via modulation of the leukocyte-endothelial interaction.