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. 1982 Oct;196(4):379–388. doi: 10.1097/00000658-198210000-00001

Role of platelets and fibrin in the healing sequence: an in vivo study of angiogenesis and collagen synthesis.

D R Knighton, T K Hunt, K K Thakral, W H Goodson 3rd
PMCID: PMC1352693  PMID: 6181748

Abstract

The signals that initiate repair are poorly characterized. These studies investigate the capacity of platelets and fibrin to initiate angiogenesis, fibroplasia, collagen synthesis and monocyte migration in the rabbit cornea assay. Methods: Autologous platelets and platelet-free fibrin were isolated from rabbit blood. Released and control platelet preparations and autologous and commercial fibrin were implanted in rabbit corneas. Results: Thrombin-released platelets produced angiogenesis and opacification. Histology showed fibroplasia, corneal thickening, and neovascularization. Collagen synthesis was elevated to twice control levels in thrombin-activated platelet preparations. Various control platelet preparations produced no angiogenesis, no opacification, and no histologic change. All fibrin injections elicited a cellular exudate from the limbal vessels, followed by angiogenesis and corneal opacification. Histology showed a mononuclear infiltrate with neovascularization and fibroplasia. Control injections of rabbit skin collagen and fibroblasts produced no response.

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Selected References

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  1. Antoniades H. N. Human platelet-derived growth factor (PDGF): purification of PDGF-I and PDGF-II and separation of their reduced subunits. Proc Natl Acad Sci U S A. 1981 Dec;78(12):7314–7317. doi: 10.1073/pnas.78.12.7314. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Antoniades H. N., Scher C. D., Stiles C. D. Purification of human platelet-derived growth factor. Proc Natl Acad Sci U S A. 1979 Apr;76(4):1809–1813. doi: 10.1073/pnas.76.4.1809. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Ausprunk D. H., Folkman J. Migration and proliferation of endothelial cells in preformed and newly formed blood vessels during tumor angiogenesis. Microvasc Res. 1977 Jul;14(1):53–65. doi: 10.1016/0026-2862(77)90141-8. [DOI] [PubMed] [Google Scholar]
  4. Burke J. M., Ross R. Collagen synthesis by monkey arterial smooth muscle cells during proliferation and quiescence in culture. Exp Cell Res. 1977 Jul;107(2):387–395. doi: 10.1016/0014-4827(77)90360-3. [DOI] [PubMed] [Google Scholar]
  5. Castor C. W., Bignall M. C., Hossler P. A., Roberts D. J. Connective tissue activation. XXI. Regulation of glycosaminoglycan metabolism by lymphocyte (CTAP-I) and platelet (CTAP-III) growth factors. In Vitro. 1981 Sep;17(9):777–785. doi: 10.1007/BF02618444. [DOI] [PubMed] [Google Scholar]
  6. Clark R. A., Stone R. D., Leung D. Y., Silver I., Hohn D. C., Hunt T. K. Role of macrophages in would healing. Surg Forum. 1976;27(62):16–18. [PubMed] [Google Scholar]
  7. Colvin R. B., Johnson R. A., Mihm M. C., Jr, Dvorak H. F. Role of the clotting system in cell-mediated hypersensitivity. I. Fibrin deposition in delayed skin reactions in man. J Exp Med. 1973 Sep 1;138(3):686–698. doi: 10.1084/jem.138.3.686. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. D'Amore P. First annual Lamport award manuscript. Platelet--endothelial interaction and the maintenance of the microvasculature. Microvasc Res. 1978 Jan;15(1):137–145. doi: 10.1016/0026-2862(78)90014-6. [DOI] [PubMed] [Google Scholar]
  9. Deuel T. F., Huang J. S., Proffitt R. T., Baenziger J. U., Chang D., Kennedy B. B. Human platelet-derived growth factor. Purification and resolution into two active protein fractions. J Biol Chem. 1981 Sep 10;256(17):8896–8899. [PubMed] [Google Scholar]
  10. Greenburg G. B., Hunt T. K. The proliferative response in vitro of vascular endothelial and smooth muscle cells exposed to wound fluids and macrophages. J Cell Physiol. 1978 Dec;97(3 Pt 1):353–360. doi: 10.1002/jcp.1040970310. [DOI] [PubMed] [Google Scholar]
  11. Heldin C. H., Westermark B., Wasteson A. Specific receptors for platelet-derived growth factor on cells derived from connective tissue and glia. Proc Natl Acad Sci U S A. 1981 Jun;78(6):3664–3668. doi: 10.1073/pnas.78.6.3664. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kay A. B., Pepper D. S., Ewart M. R. Generation of chemotactic activity for leukocytes by the action of thrombin on human fibrinogen. Nat New Biol. 1973 May 9;243(123):56–57. [PubMed] [Google Scholar]
  13. Leibovich S. J. Production of macrophage-dependent fibroblast-stimulating activity (M-FSA) by murine macrophages. Effects on BALBc 3T3 fibroblasts. Exp Cell Res. 1978 Apr;113(1):47–56. doi: 10.1016/0014-4827(78)90086-1. [DOI] [PubMed] [Google Scholar]
  14. Martin B. M., Gimbrone M. A., Jr, Unanue E. R., Cotran R. S. Stimulation of nonlymphoid mesenchymal cell proliferation by a macrophage-derived growth factor. J Immunol. 1981 Apr;126(4):1510–1515. [PubMed] [Google Scholar]
  15. McKay D. G. Participation of components of the blood coagulation system in the inflammatory response. Am J Pathol. 1972 Apr;67(1):181–210. [PMC free article] [PubMed] [Google Scholar]
  16. Nathan C. F., Murray H. W., Cohn Z. A. The macrophage as an effector cell. N Engl J Med. 1980 Sep 11;303(11):622–626. doi: 10.1056/NEJM198009113031106. [DOI] [PubMed] [Google Scholar]
  17. PETERKOFSKY B., PROCKOP D. J. A method for the simultaneous measurement of the radioactivity of proline-C14 and hydroxyproline-C14 in biological materials. Anal Biochem. 1962 Nov;4:400–406. doi: 10.1016/0003-2697(62)90141-0. [DOI] [PubMed] [Google Scholar]
  18. Polverini P. J., Cotran P. S., Gimbrone M. A., Jr, Unanue E. R. Activated macrophages induce vascular proliferation. Nature. 1977 Oct 27;269(5631):804–806. doi: 10.1038/269804a0. [DOI] [PubMed] [Google Scholar]
  19. Ross R., Glomset J., Kariya B., Harker L. A platelet-dependent serum factor that stimulates the proliferation of arterial smooth muscle cells in vitro. Proc Natl Acad Sci U S A. 1974 Apr;71(4):1207–1210. doi: 10.1073/pnas.71.4.1207. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Rutherford R. B., Ross R. Platelet factors stimulate fibroblasts and smooth muscle cells quiescent in plasma serum to proliferate. J Cell Biol. 1976 Apr;69(1):196–203. doi: 10.1083/jcb.69.1.196. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Seppä H., Grotendorst G., Seppä S., Schiffmann E., Martin G. R. Platelet-derived growth factor in chemotactic for fibroblasts. J Cell Biol. 1982 Feb;92(2):584–588. doi: 10.1083/jcb.92.2.584. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Simpson D. M., Ross R. The neutrophilic leukocyte in wound repair a study with antineutrophil serum. J Clin Invest. 1972 Aug;51(8):2009–2023. doi: 10.1172/JCI107007. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Stavenow L., Kjellström T., Malmquist J. Stimulation of collagen production in growth-arrested myocytes and fibroblasts in culture by growth factor(s) from platelets. Exp Cell Res. 1981 Dec;136(2):321–325. doi: 10.1016/0014-4827(81)90010-0. [DOI] [PubMed] [Google Scholar]
  24. Thakral K. K., Goodson W. H., 3rd, Hunt T. K. Stimulation of wound blood vessel growth by wound macrophages. J Surg Res. 1979 Apr;26(4):430–436. doi: 10.1016/0022-4804(79)90031-3. [DOI] [PubMed] [Google Scholar]
  25. Thorgeirsson G., Robertson A. L., Jr Platelet factors and the human vascular wall. Part 2. Such factors are not required for endothelial cell proliferation and migration. Atherosclerosis. 1978 Oct;31(2):231–238. doi: 10.1016/0021-9150(78)90168-5. [DOI] [PubMed] [Google Scholar]
  26. Tsukamoto Y., Helsel W. E., Wahl S. M. Macrophage production of fibronectin, a chemoattractant for fibroblasts. J Immunol. 1981 Aug;127(2):673–678. [PubMed] [Google Scholar]
  27. Uitto J. A method for studying collagen biosynthesis in human skin biopsies in vitro. Biochim Biophys Acta. 1970 Mar 24;201(3):438–445. doi: 10.1016/0304-4165(70)90163-7. [DOI] [PubMed] [Google Scholar]
  28. Unanue E. R. Secretory function of mononuclear phagocytes: a review. Am J Pathol. 1976 May;83(2):396–418. [PMC free article] [PubMed] [Google Scholar]
  29. Wall R. T., Harker L. A., Quadracci L. J., Striker G. E. Factors influencing endothelial cell proliferation in vitro. J Cell Physiol. 1978 Aug;96(2):203–213. doi: 10.1002/jcp.1040960209. [DOI] [PubMed] [Google Scholar]
  30. Wall R. T., Harker L. A., Striker G. E. Human endothelial cell migration: stimulation by a released platelet factor. Lab Invest. 1978 Nov;39(5):523–529. [PubMed] [Google Scholar]
  31. Zetter B. R., Antoniades H. N. Stimulation of human vascular endothelial cell growth by a platelet-derived growth factor and thrombin. J Supramol Struct. 1979;11(3):361–370. doi: 10.1002/jss.400110311. [DOI] [PubMed] [Google Scholar]

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