title: In vivo neutralization of P-selectin inhibits leukocyte-endothelial interactions in retinal microcirculation during ocular inflammation.
abstract: P-selectin is one of the adhesion molecules involved in leukocyte rolling during an inflammatory reaction. The aim of this study was to examine the role of P-selectin in leukocyte-endothelial interactions in retinal microcirculation during ocular inflammation, known as endotoxin-induced uveitis (EIU), in vivo. EIU was induced in Lewis rats by footpad injection of lipopolysaccharide (LPS). At the time of LPS treatment or 12 h later, anti-rat P-selectin mAb (ARP) was injected intravenously, and its effect on leukocyte behavior in the retina was studied after intravital staining with acridine orange using a scanning laser ophthalmoscope. P-selectin gene expression in the retina was also studied by a semiquantitative polymerase chain reaction (PCR) method. Administration of ARP at the time of LPS treatment significantly reduced the number of rolling leukocytes at 6 and 12 h by 68% (P < 0.05) and 83% (P < 0.01), respectively, and the number of cells infiltrating the vitreous at 48 h by 61% (P < 0.05). Interestingly, ARP significantly inhibited the vasodilation observed during EIU. In contrast, delayed administration of ARP blocked neither cellular infiltration nor vasodilation. P-selectin gene expression was upregulated during the course of EIU. In conclusion, P-selectin may significantly contribute to the development of inflammation in the early stage of endotoxin-induced ocular inflammation.
authors.affiliation: Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto, 606, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Miyamoto
authors.forename: Y
authors.initials: Y
authors.lastname: Ogura
authors.forename: M
authors.initials: M
authors.lastname: Hamada
authors.forename: H
authors.initials: H
authors.lastname: Nishiwaki
authors.forename: N
authors.initials: N
authors.lastname: Hiroshiba
authors.forename: A
authors.initials: A
authors.lastname: Tsujikawa
authors.forename: M
authors.initials: M
authors.lastname: Mandai
authors.forename: K
authors.initials: K
authors.lastname: Suzuma
authors.forename: S J
authors.initials: SJ
authors.lastname: Tojo
authors.forename: Y
authors.initials: Y
authors.lastname: Honda
mesh_terms: D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002450:Cell Communication / Q000276:immunology*; D002465:Cell Movement / Q000276:immunology; D004730:Endothelium, Vascular / Q000473:pathology* / Q000503:physiopathology; D005260:Female; D007958:Leukocyte Count; D007962:Leukocytes / Q000473:pathology*; D008833:Microcirculation / Q000473:pathology / Q000503:physiopathology; D019007:P-Selectin / Q000276:immunology* / Q000502:physiology*; D051381:Rats; D011917:Rats, Inbred Lew; D012173:Retinitis / Q000473:pathology* / Q000503:physiopathology; D014605:Uveitis / Q000473:pathology* / Q000503:physiopathology
chemical_list: D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D019007:P-Selectin