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Circulating leukocytes are thought to extravasate from venules through open interendothelial junctions. To test this paradigm, we injected N-formyl-methionyl-leucyl-phenylalanine (FMLP) intradermally in guinea pigs, harvesting tissue at 5-60 min. At FMLP-injected sites, venular endothelium developed increased surface wrinkling and variation in thickness.(More)
Tumour blood vessels differ from their normal counterparts for reasons that have received little attention. We report here that they are of at least six distinct types, we describe how each forms, and, looking forward, encourage the targeting of tumour vessel subsets that have lost their vascular endothelial growth factor-A (VEGF-A) dependency and so are(More)
Vascular permeability factor (VPF), also known as vascular endothelial growth Tactor, is a dimeric Mr 34,000†" 42,000 glycoprotein that possesses potent vascular permeability-enhancing and endothelial cell-specific mi-togcnic activities. It is synthesized by many rodent and human tumor cells and also by some normal cells. Recently we developed a sensitive(More)
The vascular system has the critical function of supplying tissues with nutrients and clearing waste products. To accomplish these goals, the vasculature must be sufficiently permeable to allow the free, bidirectional passage of small molecules and gases and, to a lesser extent, of plasma proteins. Physiologists and many vascular biologists differ as to the(More)
In contrast to normal microvessels, those that supply tumors are strikingly hyperpermeable to circulating macromolecules such as plasma proteins. This leakiness is largely attributable to a tumor-secreted cytokine, vascular permeability factor (VPF). Tracer studies have shown that macromolecules cross tumor vascular endothelium by way of a recently(More)
Two human molecules with surprisingly similar molecular structures, LFA-1 and Mac-1/OKM1, have recently been found to be important in cytolytic T lymphocyte-mediated killing, and in complement receptor function, respectively. Human LFA-1 contains two subunits of Mr 177,000 and 95,000 (1), and OKM 1/ Mac-1 (2) has two polypeptides of strikingly similar size.(More)
Vascular permeability factor (VPF) is a highly conserved 34-42-kD protein secreted by many tumor cells. Among the most potent vascular permeability-enhancing factors known, VPF is also a selective vascular endothelial cell mitogen, and therefore has been called vascular endothelial cell growth factor (VEGF). Our goal was to define the cellular sites of VPF(More)
Vascular permeability factor/vascular endothelial growth factor (VPF/VEGF, VEGF-A) is a multifunctional cytokine with important roles in pathological angiogenesis. Using an adenoviral vector engineered to express murine VEGF-A(164), we previously investigated the steps and mechanisms by which this cytokine induced the formation of new blood vessels in adult(More)
Lymphatic vessel growth, or lymphangiogenesis, is regulated by vascular endothelial growth factor-C (VEGF-C) and -D via VEGF receptor 3 (VEGFR-3). Recent studies suggest that VEGF, which does not bind to VEGFR-3, can also induce lymphangiogenesis through unknown mechanisms. To dissect the receptor pathway that triggers VEGFR-3-independent lymphangiogenesis,(More)
Therapies directed against VEGF-A and its receptors are effective in treating many mouse tumors but have been less so in treating human cancer patients. To elucidate the reasons that might be responsible for this difference in response, we investigated the nature of the blood vessels that appear in human and mouse cancers and the tumor “surrogate” blood(More)