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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)
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)
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/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)
Many important physiological and pathological processes are modulated by angiogenesis. It has been shown that initiation of this angiogenic process is an essential early step in the progression of malignant tumors. We report here that ablation of peripheral dopaminergic nerves markedly increased angiogenesis, microvessel density, microvascular permeability,(More)
Tumors initiate angiogenesis primarily by secreting vascular endothelial growth factor (VEGF-A(164)). The first new vessels to form are greatly enlarged, pericyte-poor sinusoids, called mother vessels (MV), that originate from preexisting venules. We postulated that the venular enlargement necessary to form MV would require a selective degradation of their(More)
Vascular endothelial growth factor (VEGF)-A has essential roles in vasculogenesis and angiogenesis, but the downstream steps and mechanisms by which human VEGF-A acts are incompletely understood. We report here that human VEGF-A exerts much of its angiogenic activity by up-regulating the expression of TR3 (mouse homologue Nur77), an immediate-early response(More)