Impaired eosinophil recruitment to the cornea in P-selectin-deficient micein Onchocerca volvulus keratitis (river blindness)

PURPOSE, A murine model of helminth-induced keratitis (river blindness) tha t 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 r ecruitment of these inflammatory cells from limbal vessels to the corneal s troma. METHODS. P- and E-selectin gene knockout (-/-) mice were immunized with ant igens extracted from the parasitic helminth Onchocera volvulus. One week af ter the last immunization, parasite antigens were injected directly into th e 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 rib. The number of cells in the cornea was determined by direct counting. RESULTS. Recruitment of eosinophils to the cornea was significantly impaire d in P-selectin(-/-) mice (63.9% fewer eosinophils on day 1 [P = 0.0015], a nd 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 ocular inflammation.