scholarly journals Elevated VEGF Levels in Pulmonary Edema Fluid and PBMCs from Patients with Acute Hantavirus Pulmonary Syndrome

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Irina Gavrilovskaya ◽  
Elena Gorbunova ◽  
Frederick Koster ◽  
Erich Mackow
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Endothelial Cells ◽  
Pulmonary Edema ◽  
Vascular Permeability ◽  
Hantavirus Pulmonary Syndrome ◽  
Acute Pulmonary Edema ◽  
Vascular Endothelial ◽  
Edema Fluid ◽  
Endothelial Growth Factor

Hantavirus pulmonary syndrome is characterized by vascular permeability, hypoxia, and acute pulmonary edema. Vascular endothelial growth factor (VEGF) is induced by hypoxia, potently induces vascular permeability, and is associated with high-altitude-induced pulmonary edema. Hantaviruses alter the normal regulation ofβ3 integrins that restrict VEGF-directed permeability and hantavirus infected endothelial cells are hyperresponsive to the permeabilizing effects of VEGF. However, the role of VEGF in acute pulmonary edema observed in HPS patients remains unclear. Here we retrospectively evaluate VEGF levels in pulmonary edema fluid (PEF), plasma, sera, and PBMCs from 31 HPS patients. VEGF was elevated in HPS patients PEF compared to controls with the highest levels observed in PEF samples from a fatal HPS case. VEGF levels were highest in PBMC samples during the first five days of hospitalization and diminished during recovery. Significantly increased PEF and PBMC VEGF levels are consistent with acute pulmonary edema observed in HPS patients and HPS disease severity. We observed substantially lower VEGF levels in a severe HPS disease survivor after extracorporeal membrane oxygenation. These findings suggest the importance of patients’ VEGF levels during HPS, support the involvement of VEGF responses in HPS pathogenesis, and suggest targeting VEGF responses as a potential therapeutic approach.

scholarly journals Ultrastructural localization of vascular permeability factor/vascular endothelial growth factor (VPF/VEGF) to the abluminal plasma membrane and vesiculovacuolar organelles of tumor microvascular endothelium.

1995 ◽  
Vol 43 (4) ◽  
pp. 381-389 ◽  
Author(s):  
Qu-Hong ◽  
J A Nagy ◽  
D R Senger ◽  
H F Dvorak ◽  
A M Dvorak
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Endothelial Cells ◽  
Plasma Membrane ◽  
Growth Factor ◽  
Vascular Permeability ◽  
Vascular Endothelial ◽  
Vascular Permeability Factor ◽  
Permeability Factor ◽  
Cytoplasmic Organelles ◽  
Endothelial Growth Factor

Vascular permeability factor/vascular endothelial growth factor (VPF/VEGF) is a cytokine secreted by many animal and human tumors, activated macrophages, keratinocytes, rheumatoid synovial cells, embryonic tissues, and by cultured epithelial and mesenchymal cell lines. It acts selectively on vascular endothelial cells to increase their permeability to circulating macromolecules and to stimulate their replication. Although not detectably expressed by vascular cells in the human and animal tumors we have studied, VPF/VEGF accumulates in the microvessels supplying tumors and certain inflammatory reactions in which VPF/VEGF is also overexpressed. Light microscopic immunohistochemistry lacked the resolution necessary to localize VPF/VEGF precisely in such vessels. Therefore, we used a pre-embedding immunocytochemical method to localize VPF/VEGF at the ultrastructural level in the new blood vessels that are elicited in the peritoneal walls of mice bearing a transplantable mouse ascites tumor of ovarian origin. Intense immunostaining for VPF/VEGF was observed on the abluminal plasma membrane of tumor-associated microvascular endothelial cells and in vesiculovacuolar organelles (VVOs) present in these same endothelial cells. (VVOs are recently described cytoplasmic organelles present in tumor vascular endothelium that provide an important pathway for extravasation of circulating macromolecules.) In contrast to labeling of the abluminal plasma membrane and VVO vesicles and vacuoles, endothelial cytoplasmic organelles, such as multivesicular bodies and Weibel-Palade bodies, and the underlying basal lamina, did not stain with antibodies to VPF/VEGF. The distribution of VPF/VEGF here described corresponds to that anticipated for high-affinity VFP/VEGF receptors, although binding of VPF/VEGF to other endothelial cell surface structures, such as plasma membrane proteoglycans, is also a possibility.

scholarly journals Overexpression of vascular permeability factor/vascular endothelial growth factor and its receptors in psoriasis.

1994 ◽  
Vol 180 (3) ◽  
pp. 1141-1146 ◽  
Author(s):  
M Detmar ◽  
L F Brown ◽  
K P Claffey ◽  
K T Yeo ◽  
O Kocher ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Endothelial Cells ◽  
Growth Factor ◽  
Vascular Permeability ◽  
Microvascular Endothelial Cells ◽  
Psoriatic Skin ◽  
Vascular Endothelial ◽  
Vascular Permeability Factor ◽  
Permeability Factor ◽  
Endothelial Growth Factor

Psoriatic skin is characterized by microvascular hyperpermeability and angioproliferation, but the mechanisms responsible are unknown. We report here that the hyperplastic epidermis of psoriatic skin expresses strikingly increased amounts of vascular permeability factor (VPF; vascular endothelial growth factor), a selective endothelial cell mitogen that enhances microvascular permeability. Moreover, two VPF receptors, kdr and flt-1, are overexpressed by papillary dermal microvascular endothelial cells. Transforming growth factor alpha (TGF-alpha), a cytokine that is also overexpressed in psoriatic epidermis, induced VPF gene expression by cultured epidermal keratinocytes. VPF secreted by TGF-alpha-stimulated keratinocytes was bioactive, as demonstrated by its mitogenic effect on dermal microvascular endothelial cells in vitro. Together, these findings suggest that TGF-alpha regulates VPF expression in psoriasis by an autocrine mechanism, leading to vascular hyperpermeability and angiogenesis. Similar mechanisms may operate in tumors and in healing skin wounds which also commonly express both VPF and TGF-alpha.

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