Role of P-selectin in endotoxin-induced uveitis.
PURPOSE: P-selectin is one of the early-reactive adhesion molecules that play a part in the rolling phase of leukocytes in cellular infiltration. The study objective was to determine whether P-selectin is involved in the development of endotoxin-induced uveitis (EIU). METHODS: Endotoxin-induced uveitis was initiated in male Lewis rats by injecting 200 micrograms lipopolysaccharide (LPS) into the foot pad. Expression of P-selectin in the iris-ciliary body was studied by immunohistochemistry using wholemounts and paraffin embedded sections of iris-ciliary body prepared at various time intervals. A monoclonal antibody (mAb) against P-selectin and a ligand for P-selectin, sialyl Lewis X oligosaccharide (SLeX-OS), was intravenously injected to evaluate the effects of selectin inhibition. The effect of treatment was evaluated by the number of infiltrated cells and protein concentration in the aqueous humor at 24 hours after LPS treatment. RESULTS: P-selectin immunoreactivities were observed in the vessels of the iris in whole iris-ciliary body mounts and on the surface of the microvascular endothelium in paraffin-embedded sections. Activity was most prominent at 15 minutes and at 5 to 7 hours after LPS treatment and was moderate from 1 to 4 hours after treatment. The selective inhibition of P-selectin significantly blocked the cellular infiltration into aqueous humor, but this infiltration was even more effectively inhibited by SLeX-OS. Protein concentration in the aqueous humor was not inhibited by selectin as much as was cellular infiltration. CONCLUSIONS: In the early phase of EIU, P-selectin may be expressed on the vascular endothelium in the iris in a biphasic pattern that modulates the rolling phase of leukocytes. The expression of this molecule may be essential for succeeding processes of cellular infiltration and may determine the subsequent states of ocular inflammation.