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Angiotropin Treatment Prevents Flap Necrosis and Enhances Dermal Regeneration in Rabbits

Angiotropin Treatment Prevents Flap Necrosis and Enhances Dermal Regeneration in Rabbits Abstract • Angiotropin is a potent angiogenesis factor isolated from the serum-free media of cultured, lectin-activated peripheral monocytes. In vitro, the purified substance stimulates migration, phenotypic differentiation, and tube formation, but not proliferation of capillary endothelial cells. When injected intradermally, angiotropin induces, in dose-dependent fashion, angiogenesis associated with skin hyperplasia. We have developed a flap model with insufficient blood supply and a model for contraction-free defect healing in rabbit skin. We show that (1) local pretreatment with angiotropin can prevent flap necrosis and (2) dermal regeneration after wounding can be augmented by angiotropin. From these results, we conclude that angiotropin might be of use as an adjuvant to healing in surgery. (Arch Surg 1989;124:693-698) References 1. Folkman J, Klagsbrun M: Angiogenic factors . Science 1987;235:442-447.Crossref 2. Hunt TK: Can repair processes be stimulated by modulators (cell growth factors, angiogenic factors, etc.) without adversely affecting normal processes? J Trauma 1984;24( (suppl 9) ):S39-S47. 3. Höckel M, Sasse J, Wissler JH: Purified monocyte-derived angiogenic substance (angiotropin) stimulates migration, phenotypic changes and 'tube formation' but not proliferation of capillary endothelial cells in vitro . J Cell Physiol 1987;133:1-13.Crossref 4. Wissler JH, Logemann E, Meyer HE, et al: Structure and function of a monocytic blood vessel morphogen (angiotropin) for angiogenesis in vivo and in vitro: A copper-containing metallo-polyribonucleo-polypeptide as a novel and unique type of monokine . Protides Biol Fluids 1986;34:525-536. 5. Höckel M, Jung W, Vaupel P, et al: Purified monocyte-derived angiogenic substance (angiotropin) induces controlled angiogenesis associated with regulated tissue proliferation in rabbit skin. J Clin Invest, in press. 6. Höckel M, Beck T, Wissler JH: Neomorphogenesis of blood vessels in rabbit skin induced by a highly purified monocyte-derived polypeptide (monocyto-angiotropin) and associated tissue reactions . Int J Tissue React 1984;6:323-331. 7. Myers MB, Cherry G: Augmentation of tissue survival by delay: An experimental study in rabbits . Plast Reconstr Surg 1967;39:397.Crossref 8. Pearl RM: A unifying theory of the delay phenomenon: Recovery from the hyperadrenergic state . Ann Plast Surg 1981;7:102-108.Crossref 9. Yannas IV, Burke JF: Design of an artificial skin: I. Basic design principles . J Biomed Mater Res 1980;14:65-81.Crossref 10. Yannas IV, Burke JF, Gordon PL, et al: Design of an artificial skin: II. Control of chemical composition . J Biomed Mater Res 1980;14:107-131.Crossref 11. Dagalakis N, Flink J, Stasikelis P, et al: Design of an artificial skin: III. Control of pore structure . J Biomed Mater Res 1980;14:511-528.Crossref 12. Burke JF, Yannas IV, Quinby WC, et al: Successful use of a physiologically acceptable artificial skin in the treatment of extensive burn injury . Ann Surg 1981;194:413-428.Crossref 13. Yannas IV, Burke JF, Orgill DP, et al: Wound tissue can utilize a polymeric template to synthesize a functional extension of skin . Science 1982;215:174-176.Crossref 14. Sporn MB, Roberts AB, Shull JH, et al: Polypeptide transforming growth factors isolated from bovine sources and used for wound healing in vivo . Science 1983;219:1329-1331.Crossref 15. Buckley A, Davidson JM, Kamerath CD, et al: Sustained release of epidermal growth factor accelerates wound repair . Proc Natl Acad Sci USA 1985;82:7340-7344.Crossref 16. Davidson JM, Klagsbrun M, Hill KE, et al: Accelerated wound repair, cell proliferation, and collagen accumulation are produced by a cartilage-derived growth factor . J Cell Biol 1985;100:1219-1227.Crossref 17. Brown GL, Curtsinger L, Brightwell JR, et al: Enhancement of epidermal regeneration by biosynthetic epidermal growth factor . J Exp Med 1986;163:1319-1324.Crossref 18. Knighton DR, Ciresi KF, Fiegel VD, et al: Classification and treatment of chronic nonhealing wounds . Ann Surg 1986;204:322-330.Crossref 19. Laato M, Niinikoski J, Lebel L, et al: Stimulation of wound healing by epidermal growth factor . Ann Surg 1986;203:379-381.Crossref 20. Lawrence WT, Norton JA, Sporn MB, et al: The reversal of an Adriamycin induced healing impairment with chemoattractants and growth factors . Ann Surg 1986;203:142-147.Crossref 21. Mustoe TA, Pierce GF, Thomason A, et al: Accelerated healing of incisional wounds in rats induced by transforming growth factor-β . Science 1987;237:1333-1336.Crossref 22. Schultz GS, White M, Mitchell R, et al: Epithelial wound healing enhanced by transforming growth factor-α and vaccinia growth factor . Science 1987;235:350-352.Crossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Surgery American Medical Association

Angiotropin Treatment Prevents Flap Necrosis and Enhances Dermal Regeneration in Rabbits

Archives of Surgery , Volume 124 (6) – Jun 1, 1989

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Publisher
American Medical Association
Copyright
Copyright © 1989 American Medical Association. All Rights Reserved.
ISSN
0004-0010
eISSN
1538-3644
DOI
10.1001/archsurg.1989.01410060059012
Publisher site
See Article on Publisher Site

Abstract

Abstract • Angiotropin is a potent angiogenesis factor isolated from the serum-free media of cultured, lectin-activated peripheral monocytes. In vitro, the purified substance stimulates migration, phenotypic differentiation, and tube formation, but not proliferation of capillary endothelial cells. When injected intradermally, angiotropin induces, in dose-dependent fashion, angiogenesis associated with skin hyperplasia. We have developed a flap model with insufficient blood supply and a model for contraction-free defect healing in rabbit skin. We show that (1) local pretreatment with angiotropin can prevent flap necrosis and (2) dermal regeneration after wounding can be augmented by angiotropin. From these results, we conclude that angiotropin might be of use as an adjuvant to healing in surgery. (Arch Surg 1989;124:693-698) References 1. Folkman J, Klagsbrun M: Angiogenic factors . Science 1987;235:442-447.Crossref 2. Hunt TK: Can repair processes be stimulated by modulators (cell growth factors, angiogenic factors, etc.) without adversely affecting normal processes? J Trauma 1984;24( (suppl 9) ):S39-S47. 3. Höckel M, Sasse J, Wissler JH: Purified monocyte-derived angiogenic substance (angiotropin) stimulates migration, phenotypic changes and 'tube formation' but not proliferation of capillary endothelial cells in vitro . J Cell Physiol 1987;133:1-13.Crossref 4. Wissler JH, Logemann E, Meyer HE, et al: Structure and function of a monocytic blood vessel morphogen (angiotropin) for angiogenesis in vivo and in vitro: A copper-containing metallo-polyribonucleo-polypeptide as a novel and unique type of monokine . Protides Biol Fluids 1986;34:525-536. 5. Höckel M, Jung W, Vaupel P, et al: Purified monocyte-derived angiogenic substance (angiotropin) induces controlled angiogenesis associated with regulated tissue proliferation in rabbit skin. J Clin Invest, in press. 6. Höckel M, Beck T, Wissler JH: Neomorphogenesis of blood vessels in rabbit skin induced by a highly purified monocyte-derived polypeptide (monocyto-angiotropin) and associated tissue reactions . Int J Tissue React 1984;6:323-331. 7. Myers MB, Cherry G: Augmentation of tissue survival by delay: An experimental study in rabbits . Plast Reconstr Surg 1967;39:397.Crossref 8. Pearl RM: A unifying theory of the delay phenomenon: Recovery from the hyperadrenergic state . Ann Plast Surg 1981;7:102-108.Crossref 9. Yannas IV, Burke JF: Design of an artificial skin: I. Basic design principles . J Biomed Mater Res 1980;14:65-81.Crossref 10. Yannas IV, Burke JF, Gordon PL, et al: Design of an artificial skin: II. Control of chemical composition . J Biomed Mater Res 1980;14:107-131.Crossref 11. Dagalakis N, Flink J, Stasikelis P, et al: Design of an artificial skin: III. Control of pore structure . J Biomed Mater Res 1980;14:511-528.Crossref 12. Burke JF, Yannas IV, Quinby WC, et al: Successful use of a physiologically acceptable artificial skin in the treatment of extensive burn injury . Ann Surg 1981;194:413-428.Crossref 13. Yannas IV, Burke JF, Orgill DP, et al: Wound tissue can utilize a polymeric template to synthesize a functional extension of skin . Science 1982;215:174-176.Crossref 14. Sporn MB, Roberts AB, Shull JH, et al: Polypeptide transforming growth factors isolated from bovine sources and used for wound healing in vivo . Science 1983;219:1329-1331.Crossref 15. Buckley A, Davidson JM, Kamerath CD, et al: Sustained release of epidermal growth factor accelerates wound repair . Proc Natl Acad Sci USA 1985;82:7340-7344.Crossref 16. Davidson JM, Klagsbrun M, Hill KE, et al: Accelerated wound repair, cell proliferation, and collagen accumulation are produced by a cartilage-derived growth factor . J Cell Biol 1985;100:1219-1227.Crossref 17. Brown GL, Curtsinger L, Brightwell JR, et al: Enhancement of epidermal regeneration by biosynthetic epidermal growth factor . J Exp Med 1986;163:1319-1324.Crossref 18. Knighton DR, Ciresi KF, Fiegel VD, et al: Classification and treatment of chronic nonhealing wounds . Ann Surg 1986;204:322-330.Crossref 19. Laato M, Niinikoski J, Lebel L, et al: Stimulation of wound healing by epidermal growth factor . Ann Surg 1986;203:379-381.Crossref 20. Lawrence WT, Norton JA, Sporn MB, et al: The reversal of an Adriamycin induced healing impairment with chemoattractants and growth factors . Ann Surg 1986;203:142-147.Crossref 21. Mustoe TA, Pierce GF, Thomason A, et al: Accelerated healing of incisional wounds in rats induced by transforming growth factor-β . Science 1987;237:1333-1336.Crossref 22. Schultz GS, White M, Mitchell R, et al: Epithelial wound healing enhanced by transforming growth factor-α and vaccinia growth factor . Science 1987;235:350-352.Crossref

Journal

Archives of SurgeryAmerican Medical Association

Published: Jun 1, 1989

References