Oligotide attenuates leukocyte-endothelial cell interaction via P-selectin in the rat mesenteric vascular bed.
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.
Scalia
R
R
Department of Physiology, Thomas Jefferson University, Philadelphia, PA 19107-6799, USA.
Gauthier
T W
TW
Murohara
T
T
Lefer
A M
AM
D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005434:Flow Cytometry; D007150:Immunohistochemistry; D007962:Leukocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008642:Mesenteric Veins / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D019007:P-Selectin / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D009838:Oligodeoxyribonucleotides; D019007:P-Selectin; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester