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Contradictory results have been reported concerning the effects of prostaglandins (PGs) on leukocyte-endothelium interactions. Therefore, we investigated the in vivo effects of PGE1, PGE2, Iloprost (a stable PGI2-analogue), and also of a combination of these PGs on leukocyte rolling and FMLP-induced leukocyte adhesion in venules of rabbit mesentery. This preparation was used because of its low level of vasoactivity, eliminating hemodynamic effects on leukocyte-endothelium interactions. The mesentery was superfused with PGs or vehicle. After 30 min FMLP was added to the PG-solution for 15 min, whereupon the tissue was superfused with the PG-solution alone for another 30 min. Neither the PGs nor the cocktail influenced leukocyte rolling. During FMLP administration leukocyte adhesion increased and leukocyte rolling decreased; adhesion was highest in the presence of PGE2. The FMLP-induced decrease in leukocyte rolling was similar in all groups. After FMLP administration had been stopped the number of adherent cells almost returned to baseline and the level of leukocyte rolling increased, the baseline level being reached only in the presence of PGE2. In conclusion, these findings indicate that the effects of PGs on leukocyte-endothelium interactions are limited.

A novel single stranded polydeoxyribonucleotide (oligotide) was studied for its ability to modulate leukocyte-endothelial cell interaction, by means of intravital microscopy in the rat mesenteric microvasculature. Superfusion of the rat mesentery with 50 microM NG-nitro-L-arginine methyl ester (L-NAME), caused a significant, time-dependent increase in leukocyte rolling and adherence compared to control rats superfused with Krebs-Henseleit solution. However, oligotide (15 mg/kg i.v.) consistently reduced the L-NAME-induced leukocyte rolling (62 +/- 14 vs. 23 +/- 3 cells/min; P < 0.02) and adherence (11 +/- 2 vs. 4 +/- 1 cells/100 microns length of venule P < 0.01), without altering systemic blood pressure or mesenteric venular shear rate. Moreover, immunohistochemical localization of P-selectin expression on mesenteric venules was significantly increased (P < 0.01) after exposure to L-NAME, which was significantly attenuated by oligotide (P < 0.05). Similar results were also obtained by flow cytometric analysis performed on rat platelets. Stimulation of rat platelets with L-NAME significantly (P < 0.05) increased the fluorescence intensity of P-selectin, while the concomitant treatment of isolated rat platelets with L-NAME plus oligotide significantly (P < 0.005) attenuated P-selectin fluorescence intensity. Our data demonstrate that in vivo administration of oligotide can reduce leukocyte rolling and adherence in the mesenteric rat microvasculature by attenuating P-selectin expression, and confirming the key role of nitric oxide as an important regulator of leukocyte-endothelial cell interaction.