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 roll ing during an inflammatory reaction. The aim of this study was to exam ine the role of P-selectin in leukocyte-endothelial interactions in re tinal microcirculation during ocular inflammation, known as endotoxin- induced uveitis (EIU), in vivo. EIU was induced in Lewis rats by footp ad injection of lipopolysaccharide (LPS). At the time of LPS treatment or 12 h later, anti-rat P-selectin mAb (ARP) was injected intravenous ly, and its effect on leukocyte behavior in the retina was studied aft er intravital staining with acridine orange using a scanning laser oph thalmoscope. P-selectin gene expression in the retina was also studied by a semiquantitative polymerase chain reaction (PCR) method. Adminis tration 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 vitr eous at 48 h by 61% (P < 0.05). Interestingly, ARP significantly inhib ited the vasodilation observed during EIU. In contrast, delayed admini stration 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 develop ment of inflammation in the early stage of endotoxin-induced ocular in flammation. (C) 1998 Academic Press.