Oncostatin M induces angiogenesis in vitro and in vivo.

Neovascularization of the atherosclerotic plaque is responsible for its weakening and consequently for the complications of vascular disease. Macrophages are a source of growth factors that can modulate angiogenesis. In this study, we analyzed the effect of oncostatin M (OSM) on angiogenesis, as it could be involved in the development of atherosclerosis. The effect of OSM was compared with those of leukemia inhibitory factor (LIF) and interleukin-6 (IL-6). On human dermal microvasculature endothelial cells (HMEC-1s), OSM (22.5 to 112.5 pmol/L) induced a dose-dependent increase in cell proliferation greater than that induced by the classic angiogenic factors vascular endothelial growth factor (VEGF; 543 pmol/L) and basic fibroblast growth factor (bFGF; 1.1 nmol/L). LIF (19 to 475 pmol/L) induced only a 30% increase in cell proliferation, and IL-6 had no effect. Furthermore, in a modified Boyden-chamber model, OSM, LIF, and IL-6 were chemoattractant for HMEC-1s. In a tridimensional gel of fibrin, OSM increased tube formation and tube length, which were already noticeable by day 3. LIF and IL-6 induced a weaker effect that was only obvious by day 10. The angiogenic effect of OSM was also demonstrated in vivo in a rabbit corneal model: OSM was more potent than LIF, the length of the neovessels being longer with OSM than with LIF, whereas IL-6 was without effect. We tested factors that could be involved in the proliferative effect of OSM on HMEC-1s. OSM induced only a slight increase in the urokinase receptor and a 60% increase in VEGF secretion, whereas it does not modify IL-8 secretion or bFGF levels. The effect of OSM seems to depend on endothelial cell origin and cell species: OSM (up to 112.5 pmol/L) did not induce human umbilical vein endothelial cell proliferation and even had a small inhibitory effect (17%) on calf pulmonary artery endothelial cells. In conclusion, OSM induces an angiogenic effect on capillary endothelial cells, which could be, at least in part, implicated in pathological processes such as atherosclerosis or tumor growth.

[1]  A. Weyrich,et al.  Oncostatin M is a proinflammatory mediator. In vivo effects correlate with endothelial cell expression of inflammatory cytokines and adhesion molecules. , 1997, The Journal of clinical investigation.

[2]  S. Ren,et al.  Human mast cells stimulate vascular tube formation. Tryptase is a novel, potent angiogenic factor. , 1997, The Journal of clinical investigation.

[3]  E. Wijelath,et al.  Oncostatin M induces basic fibroblast growth factor expression in endothelial cells and promotes endothelial cell proliferation, migration and spindle morphology. , 1997, Journal of cell science.

[4]  J. Ware,et al.  Angiogenesis in ischemic heart disease , 1997, Nature Medicine.

[5]  A. Harris,et al.  Association of macrophage infiltration with angiogenesis and prognosis in invasive breast carcinoma. , 1996, Cancer research.

[6]  M. Klagsbrun,et al.  Inhibition of Endothelial Cell Growth by Macrophage-like U-937 Cell-derived Oncostatin M, Leukemia Inhibitory Factor, and Transforming Growth Factor β1* , 1996, The Journal of Biological Chemistry.

[7]  G. Ciliberto,et al.  IL-6 is an in vitro and in vivo autocrine growth factor for middle T antigen-transformed endothelial cells. , 1996, Journal of immunology.

[8]  R. Arceci,et al.  Induction of embryonic vasculogenesis by bFGF and LIF in vitro and in vivo. , 1996, Developmental biology.

[9]  R. Sayers,et al.  Angiogenesis in abdominal aortic aneurysms. , 1996, European journal of vascular and endovascular surgery : the official journal of the European Society for Vascular Surgery.

[10]  G. Yancopoulos,et al.  Differential activation of the extracellular signal‐regulated kinase, Jun Kinase and Janus Kinase‐Stat pathways by oncostatin M and basic fibroblast growth factor in AIDS‐derived Kaposi's sarcoma cells , 1996, AIDS.

[11]  M. Centrella,et al.  Modulation of transforming growth factor beta receptor levels on microvascular endothelial cells during in vitro angiogenesis. , 1996, The Journal of clinical investigation.

[12]  L. F. Fajardo,et al.  Transforming growth factor beta1 induces angiogenesis in vivo with a threshold pattern. , 1996, Laboratory investigation; a journal of technical methods and pathology.

[13]  M. Kuzuya,et al.  Induction of angiogenesis by smooth muscle cell‐derived factor: Possible role in neovascularization in atherosclerotic plaque , 1995, Journal of cellular physiology.

[14]  T. Eberlein,et al.  T lymphocytes that infiltrate tumors and atherosclerotic plaques produce heparin-binding epidermal growth factor-like growth factor and basic fibroblast growth factor: a potential pathologic role. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[15]  B. Ensoli,et al.  Cytokines from activated T cells induce normal endothelial cells to acquire the phenotypic and functional features of AIDS-Kaposi's sarcoma spindle cells. , 1995, The Journal of clinical investigation.

[16]  L. Orci,et al.  Leukemia inhibitory factor (LIF) inhibits angiogenesis in vitro. , 1995, Journal of cell science.

[17]  J. Campbell,et al.  Human leukemia inhibitory factor inhibits development of experimental atherosclerosis. , 1994, Arteriosclerosis and thrombosis : a journal of vascular biology.

[18]  L. Mucke,et al.  Neurologic disease induced in transgenic mice by cerebral overexpression of interleukin 6. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[19]  J. Soria,et al.  [Fibrinogen, a vascular risk factor]. , 1993, Bulletin de l'Academie nationale de medecine.

[20]  M. Boguski,et al.  Linking yeast genetics to mammalian genomes: identification and mapping of the human homolog of CDC27 via the expressed sequence tag (EST) data base. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[21]  A. Nel,et al.  Oncostatin-M stimulates tyrosine protein phosphorylation in parallel with the activation of p42MAPK/ERK-2 in Kaposi's cells. Evidence that this pathway is important in Kaposi cell growth. , 1993, The Journal of clinical investigation.

[22]  L. Orci,et al.  Upregulation of urokinase receptor expression on migrating endothelial cells , 1993, The Journal of cell biology.

[23]  J. Regezi,et al.  Human immunodeficiency virus-associated oral Kaposi's sarcoma. A heterogeneous cell population dominated by spindle-shaped endothelial cells. , 1993, The American journal of pathology.

[24]  P. Kiener,et al.  Oncostatin M is a mitogen for rabbit vascular smooth muscle cells. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[25]  R. Strieter,et al.  Interleukin-8 as a macrophage-derived mediator of angiogenesis. , 1992, Science.

[26]  R. Swerlick,et al.  HMEC-1: establishment of an immortalized human microvascular endothelial cell line. , 1992, The Journal of investigative dermatology.

[27]  A. Koch,et al.  Decreased monocyte-mediated angiogenesis in scleroderma. , 1992, Clinical immunology and immunopathology.

[28]  M. Bond,et al.  The human carotid atherosclerotic plaque stimulates angiogenesis on the chick chorioallantoic membrane. , 1992, Atherosclerosis.

[29]  P. Linsley,et al.  Oncostatin M as a potent mitogen for AIDS-Kaposi's sarcoma-derived cells. , 1992, Science.

[30]  Comeau,et al.  The IL-6 signal transducer, gp130: an oncostatin M receptor and affinity converter for the LIF receptor. , 1992, Science.

[31]  S. Nakamura,et al.  Identification of a major growth factor for AIDS-Kaposi's sarcoma cells as oncostatin M. , 1992, Science.

[32]  J. Winer,et al.  Pituitary follicular cells secrete an inhibitor of aortic endothelial cell growth: identification as leukemia inhibitory factor. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[33]  J. Liu,et al.  Regulation of IL-6 expression by oncostatin M. , 1991, Journal of immunology.

[34]  T. Rose,et al.  Oncostatin M is a member of a cytokine family that includes leukemia-inhibitory factor, granulocyte colony-stimulating factor, and interleukin 6. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[35]  A. Sutton,et al.  The response of endothelial cells to TGF beta-1 is dependent upon cell shape, proliferative state and the nature of the substratum. , 1991, Journal of cell science.

[36]  G. D. Phillips,et al.  Wound healing angiogenesis: indirect stimulation by basic fibroblast growth factor. , 1990, The Journal of trauma.

[37]  D. Bani,et al.  Interleukin 1 is an autocrine regulator of human endothelial cell growth. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[38]  J. Wautier,et al.  Identification of an endothelial cell growth-inhibitory activity produced by human monocytes. , 1990, Experimental cell research.

[39]  L. Sachs,et al.  Pattern of interleukin 6 gene expression in vivo suggests a role for this cytokine in angiogenesis. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[40]  D. Goeddel,et al.  Vascular endothelial growth factor is a secreted angiogenic mitogen. , 1989, Science.

[41]  S. Brem,et al.  Angiogenic activity of the atherosclerotic carotid artery plaque. , 1989, Journal of neurosurgery.

[42]  G. Todaro,et al.  Oncostatin M: a growth regulator produced by differentiated histiocytic lymphoma cells. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[43]  A. Barger,et al.  Hypothesis: vasa vasorum and neovascularization of human coronary arteries. A possible role in the pathophysiology of atherosclerosis. , 1984, The New England journal of medicine.

[44]  M. M. Bradford.  A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. , 1976, Analytical biochemistry.

[45]  E. Jaffe,et al.  Culture of human endothelial cells derived from umbilical veins. Identification by morphologic and immunologic criteria. , 1973, The Journal of clinical investigation.