Abstract
Angiogenesis is a critical process for growth of new capillary blood vessels from preexisting capillaries and postcapillary venules, both in physiological and pathological conditions. Endothelial cell proliferation is a major component of angiogenesis and it is regulated by several growth factors. It has been previously shown that the human hemopoietic growth factor IL-3 (hIL-3), predominantly produced by activated T lymphocytes, stimulates both endothelial cell proliferation and functional activation. In the present study, we report that hIL-3 is able to induce directional migration and tube formation of HUVEC. The in vivo neoangiogenetic effect of hIL-3 was also demonstrated in a murine model in which Matrigel was used for the delivery of the cytokine, suggesting a role of hIL-3 in sustaining neoangiogenesis. Challenge of HUVEC with hIL-3 lead to the synthesis of platelet-activating factor (PAF), which was found to act as secondary mediator for hIL-3-mediated endothelial cell motility but not for endothelial cell proliferation. Consistent with the role of STAT5 proteins in regulating IL-3-mediated mitogenic signals, we herein report that, in hIL-3-stimulated HUVEC, the recruitment of STAT5A and STAT5B, by the beta common (betac) subunit of the IL-3R, was not affected by PAF receptor blockade.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Apolipoproteins D
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Apolipoproteins*
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Azepines / pharmacology
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Carrier Proteins / metabolism
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Cell Division / drug effects
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Cell Line
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Cell Movement / drug effects
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Cell Movement / physiology*
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DNA-Binding Proteins / antagonists & inhibitors
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DNA-Binding Proteins / metabolism
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Endothelium, Vascular / cytology
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Endothelium, Vascular / drug effects
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Endothelium, Vascular / metabolism
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Endothelium, Vascular / physiology*
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Female
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Glycoproteins*
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Humans
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Injections, Subcutaneous
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Interleukin-3 / administration & dosage*
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Interleukin-3 / metabolism
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Interleukin-3 / physiology*
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Macromolecular Substances
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Membrane Transport Proteins*
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Mice
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Mice, Inbred C57BL
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Milk Proteins*
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Neovascularization, Physiologic / drug effects
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Neovascularization, Physiologic / physiology*
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Platelet Activating Factor / antagonists & inhibitors
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Platelet Activating Factor / biosynthesis
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Platelet Membrane Glycoproteins / antagonists & inhibitors
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Protein Binding
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Receptors, Cell Surface*
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Receptors, G-Protein-Coupled*
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Receptors, Interleukin-3 / metabolism
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STAT5 Transcription Factor
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Trans-Activators / antagonists & inhibitors
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Trans-Activators / metabolism
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Triazoles / pharmacology
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Tumor Suppressor Proteins
Substances
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APOD protein, human
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Apolipoproteins
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Apolipoproteins D
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Azepines
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Carrier Proteins
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DNA-Binding Proteins
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Glycoproteins
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Interleukin-3
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Macromolecular Substances
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Membrane Transport Proteins
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Milk Proteins
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Platelet Activating Factor
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Platelet Membrane Glycoproteins
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Receptors, Cell Surface
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Receptors, G-Protein-Coupled
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Receptors, Interleukin-3
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STAT5 Transcription Factor
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STAT5A protein, human
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STAT5B protein, human
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Stat5a protein, mouse
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Stat5b protein, mouse
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Trans-Activators
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Triazoles
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Tumor Suppressor Proteins
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platelet activating factor receptor
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bepafant