Suppressive effects of selectin inhibitor SKK-60060 on the leucocyte infiltration during endotoxin induced uveitis.

Abstract

BACKGROUND:

It is well known that selectin is involved in the development of endotoxin induced uveitis (EIU), and has a major role in leucocyte infiltration. Recently, a novel selectin inhibitor (SKK-60060) that can block P and L selectins in vitro has been developed. This study was designed to investigate the anti-inflammatory effects of SKK-60060 on the inflammatory reaction during EIU in rats by studying leucocyte-endothelium interactions.

METHODS:

EIU was induced in Lewis rats by footpad injection of lipopolysaccharide (LPS). SKK-60060 was administered 15 minutes before LPS injection, and its suppressive effects on inflammatory leucocyte behaviour were evaluated in vivo with acridine orange digital fluorography; the diameters of retinal arteries and veins were also measured. After these studies, aqueous humour was collected to evaluate leucocyte infiltration and protein leakage.

RESULTS:

After LPS injection, rolling leucocytes were observed in major retinal veins, followed by leucocyte infiltration into the vitreous cavity. Following treatment with SKK-60060, leucocyte rolling was significantly inhibited in the retinal veins (p <0.01), and subsequent leucocyte infiltration into the vitreous cavity was also significantly suppressed (p <0.01). Retinal vasodilation was also substantially suppressed in SKK-60060 treated rats (p <0.01). Similarly, leucocyte infiltration and protein leakage into the aqueous humour were reduced significantly by SKK-60060 (p <0.01).

CONCLUSIONS:

SKK-60060 treatment significantly inhibited the inflammatory reaction induced by LPS. Its inhibitory effects on P and L-selectin resulted in suppression of leucocyte infiltration and the subsequent inflammatory reaction caused by accumulated leucocytes. The current findings suggest that SKK-60060 may be useful in the management of uveitis.

• Authors: K Yamashiro, J Kiryu, A Tsujikawa, A Nonaka, K Nishijima, H Kamizuru, K Miyamoto, Y Honda, T Jomori, Y Ogura
• Journal: The British journal of ophthalmology (Br J Ophthalmol) Vol. 87 Issue 4 Pg. 476-80 (Apr 2003) ISSN: 0007-1161 [Print] England
• PMID: 12642314 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents
• Disaccharides
• Lipopolysaccharides
• SKK 60060
• Selectins

Topics

• Animals
• Anti-Inflammatory Agents (pharmacology)
• Aqueous Humor (metabolism)
• Cell Movement (drug effects)
• Disaccharides (pharmacology)
• Disease Models, Animal
• Endothelium, Vascular (physiopathology)
• Fluoroscopy (methods)
• Image Processing, Computer-Assisted (methods)
• Leukocyte Count
• Leukocytes (drug effects, physiology)
• Lipopolysaccharides
• Rats
• Rats, Inbred Lew
• Selectins (physiology)
• Uveitis (drug therapy, metabolism, pathology, physiopathology)