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

K. Fukagawa, N. Okada, H. Fujishima, T. Nakajima, Kazuo Tsubota, Y. Takano, H. Kawasaki, H. Saito, K. Hirai

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)58-62
Number of pages5
JournalInvestigative Ophthalmology and Visual Science
Volume43
Issue number1
Publication statusPublished - 2002
Externally publishedYes

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CCR3 Receptors
CCR1 Receptors
Corneal Ulcer
Eosinophils
Hypersensitivity
Corneal Keratocytes
Chemotaxis
Tears
Antibodies
Therapeutics
CCR Receptors
Chemokine CCL5
Chemotactic Factors
Interleukin-4
Tumor Necrosis Factor-alpha

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Fukagawa, K., Okada, N., Fujishima, H., Nakajima, T., Tsubota, K., Takano, Y., ... Hirai, K. (2002). CC-chemokine receptor 3: A possible target in treatment of allergy-related corneal ulcer. Investigative Ophthalmology and Visual Science, 43(1), 58-62.

CC-chemokine receptor 3 : A possible target in treatment of allergy-related corneal ulcer. / Fukagawa, K.; Okada, N.; Fujishima, H.; Nakajima, T.; Tsubota, Kazuo; Takano, Y.; Kawasaki, H.; Saito, H.; Hirai, K.

In: Investigative Ophthalmology and Visual Science, Vol. 43, No. 1, 2002, p. 58-62.

Research output: Contribution to journalArticle

Fukagawa, K, Okada, N, Fujishima, H, Nakajima, T, Tsubota, K, Takano, Y, Kawasaki, H, Saito, H & Hirai, K 2002, 'CC-chemokine receptor 3: A possible target in treatment of allergy-related corneal ulcer', Investigative Ophthalmology and Visual Science, vol. 43, no. 1, pp. 58-62.
Fukagawa, K. ; Okada, N. ; Fujishima, H. ; Nakajima, T. ; Tsubota, Kazuo ; Takano, Y. ; Kawasaki, H. ; Saito, H. ; Hirai, K. / CC-chemokine receptor 3 : A possible target in treatment of allergy-related corneal ulcer. In: Investigative Ophthalmology and Visual Science. 2002 ; Vol. 43, No. 1. pp. 58-62.
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abstract = "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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T2 - A possible target in treatment of allergy-related corneal ulcer

AU - Fukagawa, K.

AU - Okada, N.

AU - Fujishima, H.

AU - Nakajima, T.

AU - Tsubota, Kazuo

AU - Takano, Y.

AU - Kawasaki, H.

AU - Saito, H.

AU - Hirai, K.

PY - 2002

Y1 - 2002

N2 - 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.

AB - 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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