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Matthias D. Becker, Kiera Garman, Scott M. Whitcup, Stephen R. Planck, James T. Rosenbaum; Inhibition of Leukocyte Sticking and Infiltration, but Not Rolling, by Antibodies to ICAM-1 and LFA-1 in Murine Endotoxin–Induced Uveitis. Invest. Ophthalmol. Vis. Sci. 2001;42(11):2563-2566.
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purpose. Cell-adhesion molecules are critical elements in intravascular rolling
and sticking of leukocytes during acute inflammation. In this process,
selectins are thought to be involved in initial adhesion and rolling,
and integrin–Ig superfamily interactions are believed primarily to
mediate stronger adhesion and transendothelial migration. This study
clarifies the role of two adhesion molecules, intercellular adhesion
molecule (ICAM)-1 and leukocyte functional antigen (LFA)-1, in
endotoxin-induced uveitis (EIU).
methods. Intravital microscopy was used to record the movement and location of
leukocytes in the irises of mice with uveitis induced by intravitreal
injection of 250 ng Escherichia coli endotoxin. Each
mouse concurrently received an intraperitoneal injection of monoclonal
neutralizing antibodies for ICAM-1, LFA-1, or both or control
results. Mice treated with endotoxin and control antibodies had an inflammatory
response that was clearly present at the 6- and 24-hour time points and
was mostly resolved by 48 hours. Mice that received anti-ICAM-1 or
anti-LFA-1 had significantly fewer cells infiltrating their irises at 6
and 24 hours. Detailed analysis of the 6-hour time point recordings
revealed that neither anti-ICAM-1 nor anti-LFA-1 significantly reduced
the number of leukocytes rolling on venule endothelial surfaces, but
the treatments reduced the number of firmly adherent cells.
conclusions. These data confirm previous reports that ICAM-1 and LFA-1 are important
mediators of EIU. The dynamic in vivo images clearly support the
hypothesis that integrin-mediated cell adhesion is more critical for
the firm adhesion of sticking cells than for leukocyte
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