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.