ANGIOGENESIS IN THE huPBL-SCID MODEL OF HUMAN TRANSPLANT REJECTION1

Moulton, Karen S.; Melder, Robert J.; Dharnidharka, Vikas R.; Hardin-Young, Janet; Jain, Rakesh K.; Briscoe, David M.

doi:10.1097/00007890-199906270-00020

Cited by 43 publications

(50 citation statements)

References 15 publications

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“…However, the association of inflammatory cell infiltration with angiogenesis has been established. The angiogenesis process is known to be proinflammatory due to enhanced adhesion and permeability in inflammatory lesions (21). We also found that von Willebrand factor was expressed diffusely and more intensely on large vessels as well as small vessels in affected lesions than in non-affected areas.…”

Section: Discussionsupporting

confidence: 55%

Anti-Vascular Endothelial Growth Factor Gene Therapy Attenuates Lung Injury and Fibrosis in Mice

Hamada

Kuwano

Yamada

et al. 2005

The Journal of Immunology

160

110

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Vascular endothelial growth factor (VEGF) is an angiogenesis factor with proinflammatory roles. Flt-1 is one of the specific receptors for VEGF, and soluble flt-1 (sflt-1) binds to VEGF and competitively inhibits it from binding to the receptors. We examined the role of VEGF in the pathophysiology of bleomycin-induced pneumopathy in mice, using a new therapeutic strategy that comprises transfection of the sflt-1 gene into skeletal muscles as a biofactory for anti-VEGF therapy. The serum levels of sflt-1 were significantly increased at 3–14 days after the gene transfer. Transfection of the sflt-1 gene at 3 days before or 7 days after the intratracheal instillation of bleomycin decreased the number of inflammatory cells, the protein concentration in the bronchoalveolar lavage fluid and with von Willebrand factor expression at 14 days. Transfection of the sflt-1 gene also attenuated pulmonary fibrosis and apoptosis at 14 days. Since the inflammatory cell infiltration begins at 3 days and is followed by interstitial fibrosis, it is likely that VEGF has important roles as a proinflammatory, a permeability-inducing, and an angiogenesis factor not only in the early inflammatory phase but also in the late fibrotic phase. Furthermore, this method may be beneficial for treating lung injury and fibrosis from the viewpoint of clinical application, since it does not require the use of a viral vector or neutralizing Ab.

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Section: Discussionsupporting

confidence: 55%

Anti-Vascular Endothelial Growth Factor Gene Therapy Attenuates Lung Injury and Fibrosis in Mice

Hamada

Kuwano

Yamada

et al. 2005

The Journal of Immunology

160

110

View full text Add to dashboard Cite

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“…Full-thickness human neonatal foreskin grafts were transplanted onto CB.17 SCID mice as described (4,36) and were allowed to heal for 4-6 weeks. For humanization, peripheral blood lymphocytes (PBLs) were isolated from leukapheresis packs obtained from the Blood Donor Centers at the Children's Hospital and the Dana Farber Cancer Institute (Boston, Massachusetts, USA).…”

Section: Methodsmentioning

confidence: 99%

“…Frozen specimens were fixed in acetone, and formalin-fixed specimens were deparaffined. Immunohistochemistry was performed with primary and secondary horseradish peroxidase-conjugated antibodies on frozen sections as described (4,12) and on paraffin-embedded sections using the VectaStain Kit (Vector, Burlinghame, California, USA) and the Tyramide Signal Amplification (TSA) Biotin system (NEN Life Science Products, Boston, Massachusetts, USA) according to the manufacturers' instructions. All specimens were developed in 3-amino ethylcarbazole (4,12) and were counterstained in Gill's hematoxylin.…”

Section: Figurementioning

confidence: 99%

“…This model is unique, as circulating human leukocytes in the huSCID mouse selectively interact with human endothelial cells in the skin allograft (4,36,44), allowing for the analysis of molecules involved in endothelial cell-dependent mechanisms of human leukocyte trafficking. In our model, human foreskin is transplanted onto SCID mice and is allowed to heal for 4-6 weeks.…”

Section: Function Of Vegf In Allogeneic Human Leukocyte Recruitmentmentioning

confidence: 99%

“…It is well established that leukocyte recruitment into sites of inflammation is associated with angiogenesis, and there is considerable evidence to suggest that angiogenesis and inflammation occur in an interactive and overlapping manner (1)(2)(3)(4). Vascular endothelial growth factor (VEGF) is a potent angiogenesis factor that has important roles in both normal physiological as well as pathological vasculogenesis and angiogenesis (5)(6)(7).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Proinflammatory functions of vascular endothelial growth factor in alloimmunity

Reinders¹,

Sho²,

Izawa³

et al. 2003

J. Clin. Invest.

Self Cite

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Vascular endothelial growth factor (VEGF), an established angiogenesis factor, is expressed in allografts undergoing rejection, but its function in the rejection process has not been defined. Here, we initially determined that VEGF is functional in the trafficking of human T cells into skin allografts in vivo in the humanized SCID mouse. In vitro, we found that VEGF enhanced endothelial cell expression of the chemokines monocyte chemoattractant protein 1 and IL-8, and in combination with IFN-γ synergistically induced endothelial cell production of the potent T cell chemoattractant IFN-inducible protein-10 (IP-10). Treatment of BALB/c (H-2d) recipients of fully MHC-mismatched C57BL/6 (H-2b) donor hearts with anti-VEGF markedly inhibited T cell infiltration of allografts and acute rejection. Anti-VEGF failed to inhibit T cell activation responses in vivo, but inhibited intragraft expression of several endothelial cell adhesion molecules and chemokines, including IP-10. In addition, whereas VEGF expression was increased, neovascularization was not associated with acute rejection, and treatment of allograft recipients with the angiogenesis inhibitor endostatin failed to inhibit leukocyte infiltration of the grafts. Thus, VEGF appears to be functional in acute allograft rejection via its effects on leukocyte trafficking. Together, these observations provide mechanistic insight into the proinflammatory function of VEGF in immunity

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Animal Models

Kreidberg¹

2009

Pediatric Nephrology

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ANGIOGENESIS IN THE huPBL-SCID MODEL OF HUMAN TRANSPLANT REJECTION1

Cited by 43 publications

References 15 publications

Anti-Vascular Endothelial Growth Factor Gene Therapy Attenuates Lung Injury and Fibrosis in Mice

Anti-Vascular Endothelial Growth Factor Gene Therapy Attenuates Lung Injury and Fibrosis in Mice

Proinflammatory functions of vascular endothelial growth factor in alloimmunity

Animal Models

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