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Kazumi Fukagawa, Naoko Okada, Hiroshi Fujishima, Toshiharu Nakajima, Kazuo Tsubota, Yoji Takano, Hiroshi Kawasaki, Hirohisa Saito, Koichi Hirai; CC-Chemokine Receptor 3: A Possible Target in Treatment of Allergy-Related Corneal Ulcer. Invest. Ophthalmol. Vis. Sci. 2002;43(1):58-62.
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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)-α
(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.
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