Impaired eosinophil recruitment to the cornea in P-selectin-deficient mice in Onchocerca volvulus keratitis (River blindness).
OBJECTIVE
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 direct counting.


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 ocular inflammation.
Kaifi
J T
JT
Departments of Medicine, Ophthalmology, and Pathology, Case Western Reserve University and University Hospitals of Cleveland, Cleveland, Ohio, USA.
Hall
L R
LR
Diaz
C
C
Sypek
J
J
Diaconu
E
E
Lass
J H
JH
Pearlman
E
E
D000818:Animals; D000947:Antigens, Helminth / Q000276:immunology; D001798:Blood Proteins / Q000276:immunology; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D003315:Cornea / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D004195:Disease Models, Animal; D019040:E-Selectin / Q000235:genetics / Q000502:physiology; D004797:Enzyme-Linked Immunosorbent Assay; D047091:Eosinophil Granule Proteins; D004804:Eosinophils / Q000276:immunology*; D019084:Fluorescent Antibody Technique, Indirect; D007114:Immunization; D007124:Immunoenzyme Techniques; D007073:Immunoglobulin E / Q000032:analysis; D015848:Interleukin-5 / Q000378:metabolism; D007634:Keratitis / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000276:immunology; D017181:Onchocerca volvulus / Q000276:immunology*; D015827:Onchocerciasis, Ocular / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D019007:P-Selectin / Q000235:genetics / Q000502:physiology*; D012260:Ribonucleases; D013154:Spleen / Q000166:cytology / Q000378:metabolism
D000947:Antigens, Helminth; D001798:Blood Proteins; D019040:E-Selectin; D047091:Eosinophil Granule Proteins; D015848:Interleukin-5; D019007:P-Selectin; D007073:Immunoglobulin E; D012260:Ribonucleases