Inhibition of platelet-activating factor-induced leukocyte adhesion in vivo by a leumedin.
Leumedins are a class of amino acid derivatives which have been reported to exert anti-inflammatory properties through a mechanism related to their ability to inhibit the expression of adhesion molecules on leukocytes. In the present study, the ability of an orally active leumedin (NPC 17923) to inhibit leukocyte adherence stimulated by platelet-activating factor was examined using an in vivo intravital microscopy preparation of mesenteric venules in the rat. Oral pretreatment with NPC 17923 (100 mg/kg) markedly increased the ratio of white blood cell velocity to red blood cell velocity, indicating that less force was required to displace a white blood cell from the vascular endothelium. NPC 17923 also significantly inhibited the adherence of white blood cells to the endothelium during the superfusion with platelet-activating factor. While not significantly affecting vessel diameter under basal conditions, vessels were significantly larger in NPC 17923-pretreated rats during the superfusion with platelet-activating factor. These results are consistent with the hypothesis that the anti-inflammatory properties of leumedins are at least in part due to effects on leukocyte adherence, but may also be in part attributable to effects on vascular tone.
McCafferty
D M
DM
Gastrointestinal Research Group, Faculty of Medicine, University of Calgary, Alberta, Canada.
Kubes
P
P
Wallace
J L
JL
D010129:4-Aminobenzoic Acid / Q000494:pharmacology; D000596:Amino Acids / Q000494:pharmacology*; D062365:Aminobenzoates; D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D004912:Erythrocytes / Q000187:drug effects; D005449:Fluorenes / Q000494:pharmacology*; D066298:In Vitro Techniques; D007962:Leukocytes / Q000187:drug effects*; D008297:Male; D008642:Mesenteric Veins / Q000033:anatomy & histology / Q000187:drug effects; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014699:Venules / Q000033:anatomy & histology / Q000166:cytology / Q000187:drug effects; D062366:para-Aminobenzoates
D000596:Amino Acids; D062365:Aminobenzoates; D005449:Fluorenes; D010972:Platelet Activating Factor; D062366:para-Aminobenzoates; C080621:N-(9H-(2,7-dichlorofluorenyl)-9-ethoxycarbonyl)-4-aminobenzoic acid; D010129:4-Aminobenzoic Acid