title: Human IL-3 stimulates endothelial cell motility and promotes in vivo new vessel formation.
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.
authors.affiliation: Dipartimento di Medicina Interna, Fisiopatologia Clinica, Università di Torino, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Dentelli
authors.forename: L
authors.initials: L
authors.lastname: Del Sorbo
authors.forename: A
authors.initials: A
authors.lastname: Rosso
authors.forename: A
authors.initials: A
authors.lastname: Molinar
authors.forename: G
authors.initials: G
authors.lastname: Garbarino
authors.forename: G
authors.initials: G
authors.lastname: Camussi
authors.forename: L
authors.initials: L
authors.lastname: Pegoraro
authors.forename: M F
authors.initials: MF
authors.lastname: Brizzi
mesh_terms: D000818:Animals; D001053:Apolipoproteins; D053399:Apolipoproteins D; D001381:Azepines / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D005260:Female; D006023:Glycoproteins; D006801:Humans; D007279:Injections, Subcutaneous; D007377:Interleukin-3 / Q000008:administration & dosage* / Q000378:metabolism / Q000502:physiology*; D046911:Macromolecular Substances; D026901:Membrane Transport Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D008894:Milk Proteins; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology*; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors; D011485:Protein Binding; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D016185:Receptors, Interleukin-3 / Q000378:metabolism; D050799:STAT5 Transcription Factor; D015534:Trans-Activators / Q000037:antagonists & inhibitors / Q000378:metabolism; D014230:Triazoles / Q000494:pharmacology; D025521:Tumor Suppressor Proteins
chemical_list: C024328:APOD protein, human; D001053:Apolipoproteins; D053399:Apolipoproteins D; D001381:Azepines; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D006023:Glycoproteins; D007377:Interleukin-3; D046911:Macromolecular Substances; D026901:Membrane Transport Proteins; D008894:Milk Proteins; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D016185:Receptors, Interleukin-3; D050799:STAT5 Transcription Factor; C494092:STAT5A protein, human; C494095:STAT5B protein, human; C494093:Stat5a protein, mouse; C494096:Stat5b protein, mouse; D015534:Trans-Activators; D014230:Triazoles; D025521:Tumor Suppressor Proteins; C039351:platelet activating factor receptor; C063964:bepafant