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Kenji Yamashiro, Junichi Kiryu, Akitaka Tsujikawa, Megumi Honjo, Atsushi Nonaka, Kazuaki Miyamoto, Yoshihito Honda, Hidenobu Tanihara, Yuichiro Ogura; Inhibitory Effects of Antithrombin III against Leukocyte Rolling and Infiltration during Endotoxin-Induced Uveitis in Rats. Invest. Ophthalmol. Vis. Sci. 2001;42(7):1553-1560.
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© 2015 Association for Research in Vision and Ophthalmology.
purpose. This study was designed to investigate the suppressive effects of
antithrombin (AT)III on inflammatory reactions during endotoxin-induced
uveitis (EIU) in rats by studying leukocyte–endothelium interactions.
methods. EIU was induced in Lewis rats by footpad injection of
lipopolysaccharide (LPS). ATIII was administered immediately after or
at 6 hours after LPS injection. Its suppressive effects on inflammatory
leukocyte behavior were evaluated in vivo with acridine orange digital
fluorography. Clinical signs of inflammation were also examined, and
aqueous humor (AH) was collected to evaluate leukocyte infiltration and
protein leakage. In a separate experiment, P-selectin mRNA expression
was studied in the iris-ciliary body (ICB) and the retina.
results. After treatment with ATIII, leukocyte rolling was substantially
inhibited along the retinal veins, suppressing subsequent leukocyte
infiltration into the vitreous cavity. Similarly, leukocyte
infiltration and protein leakage into the AH were significantly reduced
with ATIII treatment. The clinical grade of EIU was substantially lower
in ATIII-treated rats. In addition, delayed administration of ATIII
after EIU induction significantly attenuated these inflammatory
reactions. The levels of P-selectin mRNA expression in both ICB and
retina, which were upregulated after LPS injection, were substantially
lower in the ATIII-treated rats.
conclusions. ATIII treatment significantly inhibited inflammatory reactions induced
with LPS. Its suppressive effects on P-selectin expression could
contribute to the attenuation of leukocyte infiltration, possibly by
inhibiting leukocyte rolling. The current findings suggest that ATIII
may have a role in the management of patients with
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