The implications of the upregulation of ICAM-1/VCAM-1 expression of corneal fibroblasts on the pathogenesis of allergic keratopathy

Naoko Okada, Kazumi Fukagawa, Yoji Takano, Murat Dogru, Kazuo Tsubota, Hiroshi Fujishima, Kenji Matsumoto, Toshiharu Nakajima, Hirohisa Saito

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

OBJECTIVE. The present study investigated the expression of ICAM-1 and VCAM-1 on fibroblasts with interleukin (IL)4 and/or tumor necrosis factor (TNF)-α stimulation and assessed the effect of eosinophil adhesion on fibroblast viability. METHODS. Primary cultured human corneal fibroblasts were incubated with IL-4, TNF-α, or their combination for 24 hours. Expression of ICAM-1 and VCAM-1 was examined by real-time quantitative PCR and flow cytometric analysis. Purified eosinophils were cocultured with activated fibroblasts, and the number of eosinophils adhered to fibroblasts and the number of damaged fibroblasts were counted using microscopy. In a separate trial, conjunctival and corneal impression cytology was performed on patients with atopic keratoconjunctivitis and corneal ulcers (eight eyes) to assess the status of the ocular surface epithelium and the presence of inflammatory cell infiltrates. RESULTS. Real-time quantitative PCR and flow cytometric analysis revealed that both mRNA and protein of VCAM-1 and ICAM-1 were upregulated by IL-4 and TNF-α. IL-5-primed eosinophils adhered to the corneal fibroblasts treated with IL-4 and TNF-α, and the fibroblasts were damaged by eosinophil adherence. Anti-ICAM-1 antibody and anti-VCAM-1 antibody inhibited the eosinophil adherence to fibroblasts and the fibroblast damage. Impression cytology revealed extensive infiltration of neutrophil and eosinophils among isolated ocular surface epithelial cells with advanced squamous metaplasia. CONCLUSIONS. Corneal fibroblasts expressed ICAM-1 and VCAM-1 when activated with IL-4 and TNF-α. Eosinophils can adhere to the activated fibroblasts and can induce subsequent fibroblast damage through these adhesion molecules. Eosinophil adhesion to fibroblasts may possibly contribute to the pathogenesis of severe persistent allergic corneal ulcers.

Original languageEnglish
Pages (from-to)4512-4518
Number of pages7
JournalInvestigative Ophthalmology and Visual Science
Volume46
Issue number12
DOIs
Publication statusPublished - 2005 Dec

Fingerprint

Vascular Cell Adhesion Molecule-1
Intercellular Adhesion Molecule-1
Up-Regulation
Fibroblasts
Eosinophils
Interleukin-4
Tumor Necrosis Factor-alpha
Corneal Ulcer
Cell Biology
Real-Time Polymerase Chain Reaction
Keratoconjunctivitis
Neutrophil Infiltration
Interleukin-5
Metaplasia
Microscopy
Anti-Idiotypic Antibodies

ASJC Scopus subject areas

  • Ophthalmology

Cite this

The implications of the upregulation of ICAM-1/VCAM-1 expression of corneal fibroblasts on the pathogenesis of allergic keratopathy. / Okada, Naoko; Fukagawa, Kazumi; Takano, Yoji; Dogru, Murat; Tsubota, Kazuo; Fujishima, Hiroshi; Matsumoto, Kenji; Nakajima, Toshiharu; Saito, Hirohisa.

In: Investigative Ophthalmology and Visual Science, Vol. 46, No. 12, 12.2005, p. 4512-4518.

Research output: Contribution to journalArticle

Okada, Naoko ; Fukagawa, Kazumi ; Takano, Yoji ; Dogru, Murat ; Tsubota, Kazuo ; Fujishima, Hiroshi ; Matsumoto, Kenji ; Nakajima, Toshiharu ; Saito, Hirohisa. / The implications of the upregulation of ICAM-1/VCAM-1 expression of corneal fibroblasts on the pathogenesis of allergic keratopathy. In: Investigative Ophthalmology and Visual Science. 2005 ; Vol. 46, No. 12. pp. 4512-4518.
@article{f31a962439b849bdbb7827a32c161311,
title = "The implications of the upregulation of ICAM-1/VCAM-1 expression of corneal fibroblasts on the pathogenesis of allergic keratopathy",
abstract = "OBJECTIVE. The present study investigated the expression of ICAM-1 and VCAM-1 on fibroblasts with interleukin (IL)4 and/or tumor necrosis factor (TNF)-α stimulation and assessed the effect of eosinophil adhesion on fibroblast viability. METHODS. Primary cultured human corneal fibroblasts were incubated with IL-4, TNF-α, or their combination for 24 hours. Expression of ICAM-1 and VCAM-1 was examined by real-time quantitative PCR and flow cytometric analysis. Purified eosinophils were cocultured with activated fibroblasts, and the number of eosinophils adhered to fibroblasts and the number of damaged fibroblasts were counted using microscopy. In a separate trial, conjunctival and corneal impression cytology was performed on patients with atopic keratoconjunctivitis and corneal ulcers (eight eyes) to assess the status of the ocular surface epithelium and the presence of inflammatory cell infiltrates. RESULTS. Real-time quantitative PCR and flow cytometric analysis revealed that both mRNA and protein of VCAM-1 and ICAM-1 were upregulated by IL-4 and TNF-α. IL-5-primed eosinophils adhered to the corneal fibroblasts treated with IL-4 and TNF-α, and the fibroblasts were damaged by eosinophil adherence. Anti-ICAM-1 antibody and anti-VCAM-1 antibody inhibited the eosinophil adherence to fibroblasts and the fibroblast damage. Impression cytology revealed extensive infiltration of neutrophil and eosinophils among isolated ocular surface epithelial cells with advanced squamous metaplasia. CONCLUSIONS. Corneal fibroblasts expressed ICAM-1 and VCAM-1 when activated with IL-4 and TNF-α. Eosinophils can adhere to the activated fibroblasts and can induce subsequent fibroblast damage through these adhesion molecules. Eosinophil adhesion to fibroblasts may possibly contribute to the pathogenesis of severe persistent allergic corneal ulcers.",
author = "Naoko Okada and Kazumi Fukagawa and Yoji Takano and Murat Dogru and Kazuo Tsubota and Hiroshi Fujishima and Kenji Matsumoto and Toshiharu Nakajima and Hirohisa Saito",
year = "2005",
month = "12",
doi = "10.1167/iovs.04-1494",
language = "English",
volume = "46",
pages = "4512--4518",
journal = "Investigative Ophthalmology and Visual Science",
issn = "0146-0404",
publisher = "Association for Research in Vision and Ophthalmology Inc.",
number = "12",

}

TY - JOUR

T1 - The implications of the upregulation of ICAM-1/VCAM-1 expression of corneal fibroblasts on the pathogenesis of allergic keratopathy

AU - Okada, Naoko

AU - Fukagawa, Kazumi

AU - Takano, Yoji

AU - Dogru, Murat

AU - Tsubota, Kazuo

AU - Fujishima, Hiroshi

AU - Matsumoto, Kenji

AU - Nakajima, Toshiharu

AU - Saito, Hirohisa

PY - 2005/12

Y1 - 2005/12

N2 - OBJECTIVE. The present study investigated the expression of ICAM-1 and VCAM-1 on fibroblasts with interleukin (IL)4 and/or tumor necrosis factor (TNF)-α stimulation and assessed the effect of eosinophil adhesion on fibroblast viability. METHODS. Primary cultured human corneal fibroblasts were incubated with IL-4, TNF-α, or their combination for 24 hours. Expression of ICAM-1 and VCAM-1 was examined by real-time quantitative PCR and flow cytometric analysis. Purified eosinophils were cocultured with activated fibroblasts, and the number of eosinophils adhered to fibroblasts and the number of damaged fibroblasts were counted using microscopy. In a separate trial, conjunctival and corneal impression cytology was performed on patients with atopic keratoconjunctivitis and corneal ulcers (eight eyes) to assess the status of the ocular surface epithelium and the presence of inflammatory cell infiltrates. RESULTS. Real-time quantitative PCR and flow cytometric analysis revealed that both mRNA and protein of VCAM-1 and ICAM-1 were upregulated by IL-4 and TNF-α. IL-5-primed eosinophils adhered to the corneal fibroblasts treated with IL-4 and TNF-α, and the fibroblasts were damaged by eosinophil adherence. Anti-ICAM-1 antibody and anti-VCAM-1 antibody inhibited the eosinophil adherence to fibroblasts and the fibroblast damage. Impression cytology revealed extensive infiltration of neutrophil and eosinophils among isolated ocular surface epithelial cells with advanced squamous metaplasia. CONCLUSIONS. Corneal fibroblasts expressed ICAM-1 and VCAM-1 when activated with IL-4 and TNF-α. Eosinophils can adhere to the activated fibroblasts and can induce subsequent fibroblast damage through these adhesion molecules. Eosinophil adhesion to fibroblasts may possibly contribute to the pathogenesis of severe persistent allergic corneal ulcers.

AB - OBJECTIVE. The present study investigated the expression of ICAM-1 and VCAM-1 on fibroblasts with interleukin (IL)4 and/or tumor necrosis factor (TNF)-α stimulation and assessed the effect of eosinophil adhesion on fibroblast viability. METHODS. Primary cultured human corneal fibroblasts were incubated with IL-4, TNF-α, or their combination for 24 hours. Expression of ICAM-1 and VCAM-1 was examined by real-time quantitative PCR and flow cytometric analysis. Purified eosinophils were cocultured with activated fibroblasts, and the number of eosinophils adhered to fibroblasts and the number of damaged fibroblasts were counted using microscopy. In a separate trial, conjunctival and corneal impression cytology was performed on patients with atopic keratoconjunctivitis and corneal ulcers (eight eyes) to assess the status of the ocular surface epithelium and the presence of inflammatory cell infiltrates. RESULTS. Real-time quantitative PCR and flow cytometric analysis revealed that both mRNA and protein of VCAM-1 and ICAM-1 were upregulated by IL-4 and TNF-α. IL-5-primed eosinophils adhered to the corneal fibroblasts treated with IL-4 and TNF-α, and the fibroblasts were damaged by eosinophil adherence. Anti-ICAM-1 antibody and anti-VCAM-1 antibody inhibited the eosinophil adherence to fibroblasts and the fibroblast damage. Impression cytology revealed extensive infiltration of neutrophil and eosinophils among isolated ocular surface epithelial cells with advanced squamous metaplasia. CONCLUSIONS. Corneal fibroblasts expressed ICAM-1 and VCAM-1 when activated with IL-4 and TNF-α. Eosinophils can adhere to the activated fibroblasts and can induce subsequent fibroblast damage through these adhesion molecules. Eosinophil adhesion to fibroblasts may possibly contribute to the pathogenesis of severe persistent allergic corneal ulcers.

UR - http://www.scopus.com/inward/record.url?scp=33644792338&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33644792338&partnerID=8YFLogxK

U2 - 10.1167/iovs.04-1494

DO - 10.1167/iovs.04-1494

M3 - Article

C2 - 16303942

AN - SCOPUS:33644792338

VL - 46

SP - 4512

EP - 4518

JO - Investigative Ophthalmology and Visual Science

JF - Investigative Ophthalmology and Visual Science

SN - 0146-0404

IS - 12

ER -