Dual role of vascular endothelial growth factor in experimental obliterative bronchiolitis

Rainer Krebs, Jussi M Tikkanen, Antti I Nykänen, Jeanette Wood, Michael Jeltsch, Seppo Ylä-Herttuala, Petri K Koskinen, Karl Lemström

Tutkimustuotos: ArtikkelijulkaisuArtikkeliTieteellinenvertaisarvioitu

Kuvaus

Obliterative bronchiolitis (OB) is the major limitation for long-term survival of lung allograft recipients. We investigated the role of vascular endothelial growth factor (VEGF) in the development of OB in rat tracheal allografts. In nonimmunosuppressed allografts, VEGF mRNA and protein expression vanished in the epithelium and increased in smooth muscle cells and mononuclear inflammatory cells with progressive loss of epithelium and airway occlusion compared with syngeneic grafts. Intragraft VEGF overexpression by adenoviral transfer of a mouse VEGF(164) gene increased early epithelial cell proliferation and regeneration but increased microvascular remodeling and lymphangiogenesis and luminal occlusion by more than 50% compared with AdiacZ-treated allografts. Although VEGF receptor inhibition decreased early epithelial regeneration in noninfected allografts, it reduced microvascular remodeling, lymphangiogenesis, intragraft traffic of CD4+ and CD8+ T cells, and the degree of luminal occlusion. Simultaneous VEGF gene transfer and platelet-derived growth factor receptor inhibition with imatinib preserved respiratory epithelium and totally prevented luminal occlusion. In conclusion, our findings indicate that VEGF has a dual role in transplant OB. Our results suggest that VEGF may protect epithelial integrity. On the other hand, VEGF may enhance luminal occlusion by increasing the recruitment of mononuclear inflammatory cells with plate let-derived growth factor acting as a final effector molecule in this process.
Alkuperäiskielienglanti
LehtiAmerican Journal of Respiratory and Critical Care Medicine
Vuosikerta171
Numero12
Sivut1421-1429
Sivumäärä9
ISSN1073-449X
DOI - pysyväislinkit
TilaJulkaistu - 2005
OKM-julkaisutyyppiA1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä, vertaisarvioitu

Lainaa tätä

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title = "Dual role of vascular endothelial growth factor in experimental obliterative bronchiolitis",
abstract = "Obliterative bronchiolitis (OB) is the major limitation for long-term survival of lung allograft recipients. We investigated the role of vascular endothelial growth factor (VEGF) in the development of OB in rat tracheal allografts. In nonimmunosuppressed allografts, VEGF mRNA and protein expression vanished in the epithelium and increased in smooth muscle cells and mononuclear inflammatory cells with progressive loss of epithelium and airway occlusion compared with syngeneic grafts. Intragraft VEGF overexpression by adenoviral transfer of a mouse VEGF(164) gene increased early epithelial cell proliferation and regeneration but increased microvascular remodeling and lymphangiogenesis and luminal occlusion by more than 50{\%} compared with AdiacZ-treated allografts. Although VEGF receptor inhibition decreased early epithelial regeneration in noninfected allografts, it reduced microvascular remodeling, lymphangiogenesis, intragraft traffic of CD4+ and CD8+ T cells, and the degree of luminal occlusion. Simultaneous VEGF gene transfer and platelet-derived growth factor receptor inhibition with imatinib preserved respiratory epithelium and totally prevented luminal occlusion. In conclusion, our findings indicate that VEGF has a dual role in transplant OB. Our results suggest that VEGF may protect epithelial integrity. On the other hand, VEGF may enhance luminal occlusion by increasing the recruitment of mononuclear inflammatory cells with plate let-derived growth factor acting as a final effector molecule in this process.",
author = "Rainer Krebs and Tikkanen, {Jussi M} and Nyk{\"a}nen, {Antti I} and Jeanette Wood and Michael Jeltsch and Seppo Yl{\"a}-Herttuala and Koskinen, {Petri K} and Karl Lemstr{\"o}m",
year = "2005",
doi = "10.1164/rccm.200408-1001OC",
language = "English",
volume = "171",
pages = "1421--1429",
journal = "American Journal of Respiratory and Critical Care Medicine",
issn = "1073-449X",
publisher = "American Thoracic Society",
number = "12",

}

Dual role of vascular endothelial growth factor in experimental obliterative bronchiolitis. / Krebs, Rainer; Tikkanen, Jussi M; Nykänen, Antti I; Wood, Jeanette; Jeltsch, Michael; Ylä-Herttuala, Seppo; Koskinen, Petri K; Lemström, Karl.

julkaisussa: American Journal of Respiratory and Critical Care Medicine, Vuosikerta 171, Nro 12, 2005, s. 1421-1429.

Tutkimustuotos: ArtikkelijulkaisuArtikkeliTieteellinenvertaisarvioitu

TY - JOUR

T1 - Dual role of vascular endothelial growth factor in experimental obliterative bronchiolitis

AU - Krebs, Rainer

AU - Tikkanen, Jussi M

AU - Nykänen, Antti I

AU - Wood, Jeanette

AU - Jeltsch, Michael

AU - Ylä-Herttuala, Seppo

AU - Koskinen, Petri K

AU - Lemström, Karl

PY - 2005

Y1 - 2005

N2 - Obliterative bronchiolitis (OB) is the major limitation for long-term survival of lung allograft recipients. We investigated the role of vascular endothelial growth factor (VEGF) in the development of OB in rat tracheal allografts. In nonimmunosuppressed allografts, VEGF mRNA and protein expression vanished in the epithelium and increased in smooth muscle cells and mononuclear inflammatory cells with progressive loss of epithelium and airway occlusion compared with syngeneic grafts. Intragraft VEGF overexpression by adenoviral transfer of a mouse VEGF(164) gene increased early epithelial cell proliferation and regeneration but increased microvascular remodeling and lymphangiogenesis and luminal occlusion by more than 50% compared with AdiacZ-treated allografts. Although VEGF receptor inhibition decreased early epithelial regeneration in noninfected allografts, it reduced microvascular remodeling, lymphangiogenesis, intragraft traffic of CD4+ and CD8+ T cells, and the degree of luminal occlusion. Simultaneous VEGF gene transfer and platelet-derived growth factor receptor inhibition with imatinib preserved respiratory epithelium and totally prevented luminal occlusion. In conclusion, our findings indicate that VEGF has a dual role in transplant OB. Our results suggest that VEGF may protect epithelial integrity. On the other hand, VEGF may enhance luminal occlusion by increasing the recruitment of mononuclear inflammatory cells with plate let-derived growth factor acting as a final effector molecule in this process.

AB - Obliterative bronchiolitis (OB) is the major limitation for long-term survival of lung allograft recipients. We investigated the role of vascular endothelial growth factor (VEGF) in the development of OB in rat tracheal allografts. In nonimmunosuppressed allografts, VEGF mRNA and protein expression vanished in the epithelium and increased in smooth muscle cells and mononuclear inflammatory cells with progressive loss of epithelium and airway occlusion compared with syngeneic grafts. Intragraft VEGF overexpression by adenoviral transfer of a mouse VEGF(164) gene increased early epithelial cell proliferation and regeneration but increased microvascular remodeling and lymphangiogenesis and luminal occlusion by more than 50% compared with AdiacZ-treated allografts. Although VEGF receptor inhibition decreased early epithelial regeneration in noninfected allografts, it reduced microvascular remodeling, lymphangiogenesis, intragraft traffic of CD4+ and CD8+ T cells, and the degree of luminal occlusion. Simultaneous VEGF gene transfer and platelet-derived growth factor receptor inhibition with imatinib preserved respiratory epithelium and totally prevented luminal occlusion. In conclusion, our findings indicate that VEGF has a dual role in transplant OB. Our results suggest that VEGF may protect epithelial integrity. On the other hand, VEGF may enhance luminal occlusion by increasing the recruitment of mononuclear inflammatory cells with plate let-derived growth factor acting as a final effector molecule in this process.

U2 - 10.1164/rccm.200408-1001OC

DO - 10.1164/rccm.200408-1001OC

M3 - Article

VL - 171

SP - 1421

EP - 1429

JO - American Journal of Respiratory and Critical Care Medicine

JF - American Journal of Respiratory and Critical Care Medicine

SN - 1073-449X

IS - 12

ER -