VEGF(164(165)) as the pathological isoform: Differential leukocyte and endothelial responses through VEGFR1 and VEGFR2

T Usui, S Isbida, K Yamasbiro, Y Kaji, V Poulaki, Johnny Moore, Tara Moore, DT Shima, AP Adamis

Research output: Contribution to journalArticle

Abstract

PURPOSE. Vascular endothelial growth factor (VEGF) induces angiogenesis and vascular permeability and is thought to be operative in several ocular vascular diseases. The VEGF isoforms are highly conserved among species; however, little is known about their differential biological functions in adult tissue. In the current study, the inflammatory potential of two prevalent VEGF isoform splice variants, WGF(120(121)) and VEGF(164(165)), was studied in the transparent and avascular adult mouse cornea. METHODS. Controlled-release pellets containing equimolar amounts of VEGF(120) and VEGF(164) were implanted in corneas. The mechanisms underlying this differential response of VEGF isoforms were explored. The response of VEGF in cultured endothelial cells was determined by Western blot analysis. The response of VEGF isoforms in leukocytes was also investigated. RESULTS. VEGF(164) was found to be significantly more potent at inducing inflammation. In vivo blockade of VEGF receptor (VEGFR)-1 significantly suppressed VEGF(164)-induced corneal inflammation. In vitro, VEGF(165) more potently stimulated intracellular adhesion molecule (ICAM)-1expression on endothelial cells, an effect that was mediated by VEGFR2. VEGF(164) was also more potent at inducing the chemotaxis of monocytes, an effect that was mediated by VEGFR1. In an immortalized human leukocyte cell line, VEGF(165) was found to induce tyrosine phosphorylation of VEGFR1 more efficiently. CONCLUSIONS. Taken together, these data identify VEGF(164(165)) as a proinflammatory isoform. and identify multiple mechanisms underlying its proinflammatory biology.
LanguageEnglish
Pages368-374
JournalINVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
Volume45
Issue number2
DOIs
Publication statusPublished - 1 Feb 2004

Fingerprint

Vascular Endothelial Growth Factor A
Protein Isoforms
Leukocytes
Cornea
human VEGFA protein
Endothelial Cells
Inflammation
Vascular Endothelial Growth Factor Receptor-1
Eye Diseases
Capillary Permeability
Chemotaxis
Vascular Diseases
Tyrosine
Monocytes
Cultured Cells
Western Blotting
Phosphorylation
Cell Line

Cite this

Usui, T ; Isbida, S ; Yamasbiro, K ; Kaji, Y ; Poulaki, V ; Moore, Johnny ; Moore, Tara ; Shima, DT ; Adamis, AP. / VEGF(164(165)) as the pathological isoform: Differential leukocyte and endothelial responses through VEGFR1 and VEGFR2. In: INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE. 2004 ; Vol. 45, No. 2. pp. 368-374.
@article{4037a84709104f21a3dcdba0494d011d,
title = "VEGF(164(165)) as the pathological isoform: Differential leukocyte and endothelial responses through VEGFR1 and VEGFR2",
abstract = "PURPOSE. Vascular endothelial growth factor (VEGF) induces angiogenesis and vascular permeability and is thought to be operative in several ocular vascular diseases. The VEGF isoforms are highly conserved among species; however, little is known about their differential biological functions in adult tissue. In the current study, the inflammatory potential of two prevalent VEGF isoform splice variants, WGF(120(121)) and VEGF(164(165)), was studied in the transparent and avascular adult mouse cornea. METHODS. Controlled-release pellets containing equimolar amounts of VEGF(120) and VEGF(164) were implanted in corneas. The mechanisms underlying this differential response of VEGF isoforms were explored. The response of VEGF in cultured endothelial cells was determined by Western blot analysis. The response of VEGF isoforms in leukocytes was also investigated. RESULTS. VEGF(164) was found to be significantly more potent at inducing inflammation. In vivo blockade of VEGF receptor (VEGFR)-1 significantly suppressed VEGF(164)-induced corneal inflammation. In vitro, VEGF(165) more potently stimulated intracellular adhesion molecule (ICAM)-1expression on endothelial cells, an effect that was mediated by VEGFR2. VEGF(164) was also more potent at inducing the chemotaxis of monocytes, an effect that was mediated by VEGFR1. In an immortalized human leukocyte cell line, VEGF(165) was found to induce tyrosine phosphorylation of VEGFR1 more efficiently. CONCLUSIONS. Taken together, these data identify VEGF(164(165)) as a proinflammatory isoform. and identify multiple mechanisms underlying its proinflammatory biology.",
author = "T Usui and S Isbida and K Yamasbiro and Y Kaji and V Poulaki and Johnny Moore and Tara Moore and DT Shima and AP Adamis",
year = "2004",
month = "2",
day = "1",
doi = "10.1167/iovs.03-0106",
language = "English",
volume = "45",
pages = "368--374",
journal = "Investigative Ophthalmology and Visual Science",
issn = "0146-0404",
number = "2",

}

VEGF(164(165)) as the pathological isoform: Differential leukocyte and endothelial responses through VEGFR1 and VEGFR2. / Usui, T; Isbida, S; Yamasbiro, K; Kaji, Y; Poulaki, V; Moore, Johnny; Moore, Tara; Shima, DT; Adamis, AP.

In: INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, Vol. 45, No. 2, 01.02.2004, p. 368-374.

Research output: Contribution to journalArticle

TY - JOUR

T1 - VEGF(164(165)) as the pathological isoform: Differential leukocyte and endothelial responses through VEGFR1 and VEGFR2

AU - Usui, T

AU - Isbida, S

AU - Yamasbiro, K

AU - Kaji, Y

AU - Poulaki, V

AU - Moore, Johnny

AU - Moore, Tara

AU - Shima, DT

AU - Adamis, AP

PY - 2004/2/1

Y1 - 2004/2/1

N2 - PURPOSE. Vascular endothelial growth factor (VEGF) induces angiogenesis and vascular permeability and is thought to be operative in several ocular vascular diseases. The VEGF isoforms are highly conserved among species; however, little is known about their differential biological functions in adult tissue. In the current study, the inflammatory potential of two prevalent VEGF isoform splice variants, WGF(120(121)) and VEGF(164(165)), was studied in the transparent and avascular adult mouse cornea. METHODS. Controlled-release pellets containing equimolar amounts of VEGF(120) and VEGF(164) were implanted in corneas. The mechanisms underlying this differential response of VEGF isoforms were explored. The response of VEGF in cultured endothelial cells was determined by Western blot analysis. The response of VEGF isoforms in leukocytes was also investigated. RESULTS. VEGF(164) was found to be significantly more potent at inducing inflammation. In vivo blockade of VEGF receptor (VEGFR)-1 significantly suppressed VEGF(164)-induced corneal inflammation. In vitro, VEGF(165) more potently stimulated intracellular adhesion molecule (ICAM)-1expression on endothelial cells, an effect that was mediated by VEGFR2. VEGF(164) was also more potent at inducing the chemotaxis of monocytes, an effect that was mediated by VEGFR1. In an immortalized human leukocyte cell line, VEGF(165) was found to induce tyrosine phosphorylation of VEGFR1 more efficiently. CONCLUSIONS. Taken together, these data identify VEGF(164(165)) as a proinflammatory isoform. and identify multiple mechanisms underlying its proinflammatory biology.

AB - PURPOSE. Vascular endothelial growth factor (VEGF) induces angiogenesis and vascular permeability and is thought to be operative in several ocular vascular diseases. The VEGF isoforms are highly conserved among species; however, little is known about their differential biological functions in adult tissue. In the current study, the inflammatory potential of two prevalent VEGF isoform splice variants, WGF(120(121)) and VEGF(164(165)), was studied in the transparent and avascular adult mouse cornea. METHODS. Controlled-release pellets containing equimolar amounts of VEGF(120) and VEGF(164) were implanted in corneas. The mechanisms underlying this differential response of VEGF isoforms were explored. The response of VEGF in cultured endothelial cells was determined by Western blot analysis. The response of VEGF isoforms in leukocytes was also investigated. RESULTS. VEGF(164) was found to be significantly more potent at inducing inflammation. In vivo blockade of VEGF receptor (VEGFR)-1 significantly suppressed VEGF(164)-induced corneal inflammation. In vitro, VEGF(165) more potently stimulated intracellular adhesion molecule (ICAM)-1expression on endothelial cells, an effect that was mediated by VEGFR2. VEGF(164) was also more potent at inducing the chemotaxis of monocytes, an effect that was mediated by VEGFR1. In an immortalized human leukocyte cell line, VEGF(165) was found to induce tyrosine phosphorylation of VEGFR1 more efficiently. CONCLUSIONS. Taken together, these data identify VEGF(164(165)) as a proinflammatory isoform. and identify multiple mechanisms underlying its proinflammatory biology.

U2 - 10.1167/iovs.03-0106

DO - 10.1167/iovs.03-0106

M3 - Article

VL - 45

SP - 368

EP - 374

JO - Investigative Ophthalmology and Visual Science

T2 - Investigative Ophthalmology and Visual Science

JF - Investigative Ophthalmology and Visual Science

SN - 0146-0404

IS - 2

ER -