In vivo neutralization of P-selectin inhibits leukocyte-endothelial interactions in retinal microcirculation during ocular inflammation.
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.
Miyamoto
K
K
Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto, 606, Japan.
Ogura
Y
Y
Hamada
M
M
Nishiwaki
H
H
Hiroshiba
N
N
Tsujikawa
A
A
Mandai
M
M
Suzuma
K
K
Tojo
S J
SJ
Honda
Y
Y
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
D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D019007:P-Selectin