Interleukin-8 as a Macrophage-Derived Mediator of Angiogenesis

• Published in: Science (American Association for the Advancement of Science) 1992-12, Vol.258 (5089), p.1798-1801
• Main Authors: Koch, Alisa E., Polverini, Peter J., Kunkel, Steven L., Harlow, Lisa A., DiPietro, Luisa A., Elner, Victor M., Elner, Susan G., Strieter, Robert M.
• Format: Article
• Language: English
• Subjects: Analysis of the immune response. Humoral and cellular immunity; Angiogenesis; Animals; Antisense oligonucleotides; Arthritis, Rheumatoid - physiopathology; Base Sequence; Biological and medical sciences; Blood; Cell Division - drug effects; Cells, Cultured; Chemotaxis; Chemotaxis - drug effects; Cornea; Cornea - drug effects; Cornea - physiology; Cytokines; Dose-Response Relationship, Drug; Endothelium, Vascular - drug effects; Endothelium, Vascular - physiology; Fibroblast Growth Factor 2 - pharmacology; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Humans; Immunobiology; Interleukin-8 - genetics; Interleukin-8 - pharmacology; Interleukins; Lymphokines, interleukins ( function, expression); Macrophages; Macrophages - physiology; Mice; Molecular Sequence Data; Monocytes; Monocytes - physiology; Neovascularization; Neovascularization, Pathologic; Neutrophils; Oligonucleotides, Antisense - pharmacology; Physiological aspects; Rabbits; Rats; Recombinant Proteins - pharmacology; Regulatory factors and their cellular receptors; Synovial Fluid - physiology; Tumor Necrosis Factor-alpha - genetics; Tumors; Umbilical Veins
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1281554

Angiogenic factors produced by monocytes-macrophages are involved in the pathogenesis of chronic inflammatory disorders characterized by persistent angiogenesis. The possibility was tested that interleukin-8 (IL-8), which is a cytokine that is chemotactic for lymphocytes and neutrophils, is also angiogenic. Human recombinant IL-8 was potently angiogenic when implanted in the rat cornea and induced proliferation and chemotaxis of human umbilical vein endothelial cells. Angiogenic activity present in the conditioned media of inflamed human rheumatoid synovial tissue macrophages or lipopolysaccharide-stimulated blood monocytes was equally blocked by antibodies to either IL-8 or tumor necrosis factor-α. An IL-8 antisense oligonucleotide specifically blocked the production of monocyte-induced angiogenic activity. These data suggest a function for macrophage-derived IL-8 in angiogenesis-dependent disorders such as rheumatoid arthritis, tumor growth, and wound repair.