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Jussuf T. Kaifi, Laurie R. Hall, Carlos Diaz, Joseph Sypek, Eugenia Diaconu, Jonathan H. Lass, Eric Pearlman; Impaired Eosinophil Recruitment to the Cornea in P-Selectin–Deficient Mice in Onchocerca volvulus Keratitis (River Blindness). Invest. Ophthalmol. Vis. Sci. 2000;41(12):3856-3861.
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purpose. A murine model of helminth-induced keratitis (river blindness) that is
characterized by a biphasic recruitment of neutrophils (days 1–3) and
eosinophils (days 3+) to the cornea has been developed. The purpose of
this study was to determine the relative contribution of P- and
E-selectin in recruitment of these inflammatory cells from limbal
vessels to the corneal stroma.
methods. P- and E-selectin gene knockout (−/−) mice were immunized with
antigens extracted from the parasitic helminth Onchocerca
volvulus. One week after the last immunization, parasite
antigens were injected directly into the corneal stroma. Mice were
killed on days 1 and 3 postchallenge, and eyes were immunostained with
either anti-eosinophil major basic protein (MBP) or with
anti-neutrophil Ab. The number of cells in the cornea was determined by
results. Recruitment of eosinophils to the cornea was significantly impaired in
P-selectin−/− mice (63.9% fewer eosinophils on day 1[ P = 0.0015], and 61% fewer on day 3[ P < 0.0001]) compared with control C57BL/6
mice. In contrast, P-selectin deficiency had no effect on neutrophil
recruitment to the cornea. There was no inhibition of eosinophil and
neutrophil migration to the corneas of E-selectin−/− mice, indicating that there is no direct role for this adhesion
molecule in helminth-induced keratitis.
conclusions. The present study demonstrates that P-selectin is an important mediator
of eosinophil recruitment to the cornea. P-selectin interactions may
therefore be potential targets for immunotherapy in eosinophil-mediated
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