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Overexpression of vascular permeability factor (VPF/VEGF) and its endothelial cell receptors in delayed hypersensitivity skin reactions.

L F Brown, S M Olbricht, B Berse, R W Jackman, G Matsueda, K A Tognazzi, E J Manseau, H F Dvorak and L Van de Water
J Immunol March 15, 1995, 154 (6) 2801-2807;
L F Brown
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S M Olbricht
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B Berse
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R W Jackman
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G Matsueda
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K A Tognazzi
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E J Manseau
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H F Dvorak
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L Van de Water
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Abstract

Delayed hypersensitivity (DH) is a T cell-mediated form of immune response characterized by a predominantly perivascular, mononuclear cell infiltrate. The venules in DH reactions are hyperpermeable to plasma proteins, leading to extravasation of plasma fibrinogen and its extravascular clotting to form a fibrin gel that promotes induration and angiogenesis. The mechanisms responsible for microvascular hyperpermeability in DH are unknown. Recently, a cytokine named vascular permeability factor (VPF, also known as vascular endothelial growth factor or VEGF) has been implicated in the chronic vascular hyperpermeability and angiogenesis of solid and ascites tumors, healing wounds, rheumatoid arthritis, and psoriasis. These findings suggested that VPF/VEGF might also have a role in the pathogenesis of DH. Two model systems were studied: allergic contact dermatitis to poison ivy in human volunteers and classical tuberculin hypersensitivity in rats. In both, in situ hybridization revealed that the mRNAs encoding VPF/VEGF were strikingly overexpressed in keratinocytes of the epidermis; scattered mononuclear cells infiltrating the dermis also overexpressed VPF/VEGF mRNA, to a greater extent in rat tuberculin than in human contact reactions. In contact reactions, mRNAs for two VPF/VEGF vascular endothelial cell receptors, flt-1 and KDR, were also strikingly overexpressed. Abundant fibrin deposition in both models confirmed that dermal microvessels were indeed hyperpermeable to plasma fibrinogen. These results implicate VPF/VEGF as a potentially important mediator in the pathogenesis of cell-mediated immunity and provide further evidence that products of epithelial cells may regulate the inflammatory response.

  • Copyright © 1995 by American Association of Immunologists
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The Journal of Immunology
Vol. 154, Issue 6
15 Mar 1995
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Overexpression of vascular permeability factor (VPF/VEGF) and its endothelial cell receptors in delayed hypersensitivity skin reactions.
L F Brown, S M Olbricht, B Berse, R W Jackman, G Matsueda, K A Tognazzi, E J Manseau, H F Dvorak, L Van de Water
The Journal of Immunology March 15, 1995, 154 (6) 2801-2807;

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Overexpression of vascular permeability factor (VPF/VEGF) and its endothelial cell receptors in delayed hypersensitivity skin reactions.
L F Brown, S M Olbricht, B Berse, R W Jackman, G Matsueda, K A Tognazzi, E J Manseau, H F Dvorak, L Van de Water
The Journal of Immunology March 15, 1995, 154 (6) 2801-2807;
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Print ISSN 0022-1767        Online ISSN 1550-6606