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E. E. Vance, S. R. Planck, J. T. Rosenbaum; CD44 Facilitates Leukocyte Extravasation in Irises of Mice with Endotoxin-Induced Uveitis. Invest. Ophthalmol. Vis. Sci. 2008;49(13):4757.
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CD44 is a cell surface receptor for hyaluronic acid, a major extracellular matrix component, and is involved in leukocyte recruitment to some sites of inflammation. In the present study, we used intravital fluorescence video microscopy to investigate the role of CD44 in leukocyte trafficking in the iris of mice with endotoxin-induced uveitis (EIU).
EIU was induced by intravitreal injection of 250 ng lipopolysaccharide (LPS) (E. coli endotoxin 055:B5) into 7 - 8 week old female BALB/c mice. At the time of LPS injection, 200 µg anti-CD44 mAb (IM7) or isotype-matched control antibodies (IgG2b) was administered by intraperitoneal (i.p.) injection. Leukocytes were labeled with Rhodamine 6G (0.27 mg) given i.p. 10 min prior to imaging. Inflammation was assessed 5 hrs post-injection by intravital fluorescence videomicroscopy of 6 - 8 iris vessels per mouse and 5 - 7 mice per treatment group. Twenty second videos were recorded and analyzed for each vessel.
Systemic treatment of EIU with anti-CD44 mAb reduced inflammation within the iris. Treatment with anti-CD44 significantly reduced leukocyte rolling along vessel walls (p = 0.03, anti-CD44 230 ± 52 rollers/min/mm2, control 820 ± 191 rollers/min/mm2) and infiltration into iris tissue (p = 0.009, anti-CD44 181 ± 50 infiltrators/mm2, control 1239 ± 229 infiltrators/mm2) versus treatment with isotype-matched control antibodies. Anti-CD44 treatment tended to decrease the density of firmly adherent leukocytes, but this trend was not significant. Hemocytometry revealed no difference in the number of viable leukocytes in the blood of anti-CD44 treated and untreated mice, thus indicating that the antibody treatment did not result in leukopenia.
The current data indicate a significant role for CD44 in the recruitment of leukocytes to inflamed mouse iris. The relative importance of CD44 with respect to other adhesion molecules and for different cell types remains to be determined and might contribute to the specificity of cell trafficking.
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