CC-chemokine receptor 3: a possible target in treatment of allergy-related corneal ulcer.

PURPOSE: To determine the suppressive effects of antibodies (Abs) against CC-chemokine receptor (CCR)-1 and CCR-3 on eosinophil chemotaxis induced by culture supernatant from corneal keratocytes and by tears from severely allergic patients with corneal ulcer.

METHODS

Primary cultures of human corneal keratocytes were incubated with interleukin (IL)-4 (33.3 ng/mL) and tumor necrosis factor (TNF)-alpha (33.3 ng/mL) for 48 hours. In tear samples collected from five severely allergic patients and three nonallergic control subjects, eosinophils were immunostained for CCR. Next, eosinophils purified from peripheral blood were preincubated with or without anti-CCR-1 and anti-CCR-3 Abs before a Boyden chamber assay was conducted. Recombinant human (rh) eotaxin, rh-regulated on activation normal T-cell expressed and secreted (rh-RANTES), culture supernatant from human corneal keratocytes, and tear samples were used as chemoattractants.

RESULTS

Eosinophils in tears from allergic patients expressed CCR-1 and -3 on their surfaces. Anti-CCR-1 and -3 Abs each inhibited eosinophil chemotaxis induced by rh-RANTES. Anti-CCR-3 Ab (but not anti-CCR-1 Ab) also inhibited eosinophil chemotaxis induced by rh-eotaxin. Anti-CCR-1 and -3 Abs, respectively, inhibited up to 75.2% and 94.6% of eosinophil chemotaxis induced by culture supernatant, as well as 27.8% and 74.5% of chemotaxis induced by tear samples.

CONCLUSIONS

Anti-CCR-1 and -3 Abs inhibited eosinophil chemotaxis induced by culture supernatant from corneal keratocytes and tear samples from severely allergic patients. Anti-CCR-3 Ab was more effective than anti-CCR-1 Ab. Inhibition of CCR-3 on eosinophils may be a treatment for corneal ulcer in patients with ocular allergy.