Vascular permeability factor: a tumor-derived polypeptide that induces endothelial cell and monocyte procoagulant activity, and promotes monocyte migration.

Clauss, Matthias; Gerlach, Marlene L.; Gerlach, Herwig; Brett, Jerold; Wang, F.; Familletti, Philip C.; Pan, Yaping; Olander, Jitka V.; Connolly, Daniel T.; Stern, David M.

doi:10.1084/jem.172.6.1535

Cited by 771 publications

(405 citation statements)

References 36 publications

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“…Nevertheless, a recent report showed that activated monocytes and even dendritic cells, which are APC present at inflamed sites, expressed only Flt-1 and not Flk-1/KDR (47)(48)(49). VEGF may thus induce monocyte activation and migration via Flt-1 (47,50). This idea is supported by the finding that during the development of CIA, infiltration of the synovial tissue by monocytes and neutrophils occurs predominantly during the acute stage (51).…”

Section: Discussionsupporting

confidence: 63%

Vascular Endothelial Growth Factor Expression and Regulation of Murine Collagen-Induced Arthritis

Kasama

Kobayashi

et al. 2000

The Journal of Immunology

130

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We have examined the expression and function of the angiogenic factor, vascular endothelial growth factor (VEGF) during the evolution of type II collagen-induced arthritis (CIA). Biologically active VEGF was expressed along a time course that paralleled the expression of two specific VEGF receptors, Flk-1 and Flt-1, and the progression of joint disease. Moreover, levels of VEGF expression correlated with the degree of neovascularization, as defined by vWF levels, and arthritis severity. Macrophage- and fibroblast-like cells, which infiltrated inflamed sites and were then activated by other inflammatory mediators, are probably important sources of VEGF and may thus regulate angiogenesis during the development of CIA. Administration of anti-VEGF antiserum to CIA mice before the onset of arthritis delayed the onset, reduced the severity, and diminished the vWF content of arthritic joints. By contrast, administration of anti-VEGF antiserum after the onset of the disease had no effect on the progression or ultimate severity of the arthritis. These data suggest that VEGF plays a crucial role during an early stage of arthritis development, affecting both neovascularization and the progression of experimentally induced synovitis.

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Section: Discussionsupporting

confidence: 63%

Vascular Endothelial Growth Factor Expression and Regulation of Murine Collagen-Induced Arthritis

Kasama

Kobayashi

et al. 2000

The Journal of Immunology

130

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“…Flt-1 is expressed by monocyte/macrophage, and VEGF can induce their migration across collagen membranes and endothelial cell monolayers (Clauss et al, 1990;Barleon et al, 1996). We showed that sFlt-1 gene transfer significantly attenuated infiltration of monocyte/macrophage both 1 and 7 days after stroke, which were associated with reduction in infarct size.…”

Section: Discussionmentioning

confidence: 99%

Postischemic Gene Transfer of Soluble Flt-1 Protects against Brain Ischemia with Marked Attenuation of Blood—Brain Barrier Permeability

Kumai

Ooboshi

Ibayashi

et al. 2006

J Cereb Blood Flow Metab

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Brain edema is a major and often mortal complication of brain ischemia. Vascular endothelial growth factor (VEGF) is also known as a potent vascular permeability factor and may play detrimental roles at the acute stage of brain infarction. Our goal in this study was to explore protective effects of gene transfer of soluble flt-1 (sFlt-1), a natural inhibitor of VEGF, on focal brain ischemia. Adenoviral vector encoding sFlt-1 or b-galactosidase as control was injected into the lateral ventricle 90 mins after photochemical distal middle cerebral artery occlusion in male spontaneously hypertensive rats. The transduced sFlt-1 was released to the cerebrospinal fluid from the ventricular wall and significantly increased 6 h, 1 and 7 days after sFlt-1 transfection. One day after brain ischemia, sFlt-1 gene transfer significantly reduced infarct volume (by 35%), brain edema (by 35%), and blood-brain barrier permeability (Evans blue extravasation; by 69%) with diminished phosphorylation of focal adhesion kinase (FAKtyr397 and FAKtyr861) in the ischemic vessels. Seven days after ischemia, sFlt-1 gene transfer also significantly attenuated infarct volume (by 29%) and monocyte/macrophage infiltration (by 27%), although there were no reductions in angiogenesis by sFlt-1 overexpression. These results suggest that sFlt-1 gene therapy targeting brain edema in acute stage of brain ischemia may be useful for brain infarction.

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“…These were termed EMAP I-III and among these, EMAP I and II were novel cytokines, 1 whereas EMAP III turned out to be identical to the previously described VEGF. 29 EMAP II is a now well-characterized proinflammatory cytokine that inhibits tumor growth and metastasis by inhibition of angiogenesis. However, the precise signaling pathways for antiangiogenic activity of EMAP II have not yet been fully elucidated.…”

Section: Discussionmentioning

confidence: 99%

Endothelial monocyte activating polypeptide II interferes with VEGF-induced proangiogenic signaling

Awasthi

Schwarz

Verma

et al. 2009

Laboratory Investigation

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Endothelial monocyte activating polypeptide II (EMAP II) is a proinflammatory cytokine with antiangiogenic properties. EMAP II functions as a potent inhibitor of primary and metastatic tumor growth, has strong inhibitory effects on endothelial cells (ECs), and can reduce intratumoral expression of the angiogenesis inducer vascular endothelial growth factor (VEGF). VEGF influences EC functions such as proliferation, migration, survival and tube formation. Therapeutic strategies that target VEGF have been demonstrated to reduce the tumor growth. We investigated the effects of EMAP II on VEGF-induced angiogenesis signaling. Primary human fetal lung ECs (HFLECs) and human umbilical vein ECs (HUVECs) were grown in E-Stim medium. Protein binding was analyzed using enzyme-linked immunosorbent assay (ELISA). Protein expression was determined by western blot analysis. EC proliferation and migration was determined using WST-1 reagent and transwell membrane, respectively. EMAP II efficiently and dose dependently binds to VEGF receptor 1 (VEGFR1) and VEGF receptor 2 (VEGFR2) as observed by ELISA. B max values for VEGFR1 and VEGFR2 were 0.45 and 0.17, respectively. In addition, EMAP II inhibited binding of VEGF to VEGFR1 and VEGFR2. EMAP II significantly reduced VEGF-induced expression of phosphorylated VEGFR1 (in HFLEC and HUVEC) by 450%, and of phosphorylated VEGFR2 (in HUVEC) by 66%. EMAP II also inhibited downstream VEGF signaling. Although VEGF-induced phosphorylation of Akt, Erk1/2, p38 and Raf 2.8-, 1.5-, 2.2-and 3.6-fold, respectively, EMAP II preincubation blocked this induction in phosphorylation to control levels. VEGF-induced EC proliferation 2.5-fold, and EMAP II pretreatment abrogated this effect. Similarly, VEGF-induced EC migration (2.5-fold) was significantly inhibited by EMAP II. These finding suggest that inhibition of VEGF signaling is one possible antiangiogenic mechanism of EMAP II, which may explain its in vivo antitumor activity and delineate therapeutic strategies to enhance anti-VEGF therapy to inhibit tumor growth.

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Vascular permeability factor: a tumor-derived polypeptide that induces endothelial cell and monocyte procoagulant activity, and promotes monocyte migration.

Cited by 771 publications

References 36 publications

Vascular Endothelial Growth Factor Expression and Regulation of Murine Collagen-Induced Arthritis

Vascular Endothelial Growth Factor Expression and Regulation of Murine Collagen-Induced Arthritis

Postischemic Gene Transfer of Soluble Flt-1 Protects against Brain Ischemia with Marked Attenuation of Blood—Brain Barrier Permeability

Endothelial monocyte activating polypeptide II interferes with VEGF-induced proangiogenic signaling

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