Distinct roles for PECAM-1, ICAM-1, and VCAM-1 in recruitment of neutrophils and eosinophils to the cornea in ocular onchocerciasis (river blindness)

Infiltration of granulocytes into the transparent mammalian cornea can resu lt in loss of corneal clarity and severe visual impairment. Since the corne a is an avascular tissue, recruitment of granulocytes such as neutrophils a nd eosinophils into the corneal stroma is initiated from peripheral (limbal ) vessels. To determine the role of vascular adhesion molecules in this pro cess, expression of platelet endothelial cell adhesion molecule 1 (PECAM-1) , ICAM-1, and VCAM-1 on limbal vessels was determined in a murine model of ocular onchocerciasis in which Ags from the parasitic worm Onchocerca volvu lus are injected into the corneal stroma. Expression of each of these molec ules was elevated after injection of parasite Ags; however, PECAM-1 and ICA M-1 expression remained elevated from 12 h after injection until 7 days, wh ereas VCAM-1 expression was more transient, with peak expression at 72 h. S ubconjunctival injection of Ab to PECAM-1 significantly inhibited neutrophi l recruitment to the cornea compared with eyes injected with control Ab (p = 0.012). Consistent with this finding, corneal opacification was significa ntly diminished (p < 0.0001). There was no significant reduction in eosinop hils. Conversely, subconjunctival injection of Ab to ICAM-1 did not impair neutrophil recruitment, but significantly inhibited eosinophil recruitment (p = 0.0032). Injection of Ab to VCAM-1 did not significantly inhibit infil tration of either cell type to the cornea. Taken together, these results de monstrate important regulatory roles for PECAM-1 and ICAM-1 in recruitment of neutrophils and eosinophils, respectively, to the cornea, and may indica te a selective approach to immune intervention.