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. 1983 Feb 1;96(2):382–385. doi: 10.1083/jcb.96.2.382

Chemotactic activity of platelet alpha granule proteins for fibroblasts

PMCID: PMC2112304  PMID: 6187750

Abstract

At sites of blood vessel injury, platelets release numerous substances that may have biological activities influencing cellular responses. In this study we examined separately the chemotactic activity for fibroblasts of three highly purified proteins obtained from platelet alpha granules: platelet factor 4 (PF4), platelet-derived growth factor (PDGF), and beta-thromboglobulin (BTG). We observed that each of these proteins was strongly chemotactic for fibroblasts, with maximum chemotactic activity in each instance comparable to that observed with an optimal concentration of the control chemotactic protein, plasma fibronectin. Each protein was active at very low concentrations. The peak chemotactic activities of PF4, PDGF, and BTG occurred at 200 mg/ml, 30 ng/ml, and 6 ng/ml, respectively. Specificity of fibroblast chemotaxis to individual platelet proteins was provided by finding that anti-PF4 immunoglobulin blocked the chemotactic activity of PF4 without affecting the chemotactic activity of PDGF, while anti-PDGF immunoglobulin blocked the activity of PDGF but did not alter the capacity of PF4 to promote fibroblast chemotaxis. These results suggest that in vivo several alpha granule proteins released from platelets may affect wound healing by causing directed fibroblast migration.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Begg G. S., Pepper D. S., Chesterman C. N., Morgan F. J. Complete covalent structure of human beta-thromboglobulin. Biochemistry. 1978 May 2;17(9):1739–1744. doi: 10.1021/bi00602a024. [DOI] [PubMed] [Google Scholar]
  2. Bowen-Pope D. F., Ross R. Platelet-derived growth factor. II. Specific binding to cultured cells. J Biol Chem. 1982 May 10;257(9):5161–5171. [PubMed] [Google Scholar]
  3. 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]
  4. Deuel T. F., Keim P. S., Farmer M., Heinrikson R. L. Amino acid sequence of human platelet factor 4. Proc Natl Acad Sci U S A. 1977 Jun;74(6):2256–2258. doi: 10.1073/pnas.74.6.2256. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Deuel T. F., Senior R. M., Chang D., Griffin G. L., Heinrikson R. L., Kaiser E. T. Platelet factor 4 is chemotactic for neutrophils and monocytes. Proc Natl Acad Sci U S A. 1981 Jul;78(7):4584–4587. doi: 10.1073/pnas.78.7.4584. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Deuel T. F., Senior R. M., Huang J. S., Griffin G. L. Chemotaxis of monocytes and neutrophils to platelet-derived growth factor. J Clin Invest. 1982 Apr;69(4):1046–1049. doi: 10.1172/JCI110509. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Goldberg I. D., Stemerman M. B., Handin R. I. Vascular permeation of platelet factor 4 after endothelial injury. Science. 1980 Aug 1;209(4456):611–612. doi: 10.1126/science.6994228. [DOI] [PubMed] [Google Scholar]
  8. Grotendorst G. R., Seppä H. E., Kleinman H. K., Martin G. R. Attachment of smooth muscle cells to collagen and their migration toward platelet-derived growth factor. Proc Natl Acad Sci U S A. 1981 Jun;78(6):3669–3672. doi: 10.1073/pnas.78.6.3669. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. 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]
  10. Hope W., Martin T. J., Chesterman C. N., Morgan F. J. Human beta-thromboglobulin inhibits PGI2 production and binds to a specific site in bovine aortic endothelial cells. Nature. 1979 Nov 8;282(5735):210–212. doi: 10.1038/282210a0. [DOI] [PubMed] [Google Scholar]
  11. Huang J. S., Huang S. S., Kennedy B., Deuel T. F. Platelet-derived growth factor. Specific binding to target cells. J Biol Chem. 1982 Jul 25;257(14):8130–8136. [PubMed] [Google Scholar]
  12. Kaplan K. L., Broekman M. J., Chernoff A., Lesznik G. R., Drillings M. Platelet alpha-granule proteins: studies on release and subcellular localization. Blood. 1979 Apr;53(4):604–618. [PubMed] [Google Scholar]
  13. Kaplan K. L., Owen J. Plasma levels of beta-thromboglobulin and platelet factor 4 as indices of platelet activation in vivo. Blood. 1981 Feb;57(2):199–202. [PubMed] [Google Scholar]
  14. Levine S. P., Krentz L. S. Development of a radioimmunoassay for human platelet factor 4. Thromb Res. 1977 Nov;11(5):673–686. doi: 10.1016/0049-3848(77)90025-1. [DOI] [PubMed] [Google Scholar]
  15. Nakao J., Ooyama T., Chang W. C., Murota S., Orimo H. Platelets stimulate aortic smooth muscle cell migration in vitro. Involvement of 12-L-hydroxy-5,8,10,14-eicosatetraenoic acid. Atherosclerosis. 1982 Jun;43(2-3):143–150. doi: 10.1016/0021-9150(82)90018-1. [DOI] [PubMed] [Google Scholar]
  16. Osterman D. G., Griffin G. L., Senior R. M., Kaiser E. T., Deuel T. F. The carboxyl-terminal tridecapeptide of platelet factor 4 is a potent chemotactic agent for monocytes. Biochem Biophys Res Commun. 1982 Jul 16;107(1):130–135. doi: 10.1016/0006-291x(82)91679-5. [DOI] [PubMed] [Google Scholar]
  17. Postlethwaite A. E., Seyer J. M., Kang A. H. Chemotactic attraction of human fibroblasts to type I, II, and III collagens and collagen-derived peptides. Proc Natl Acad Sci U S A. 1978 Feb;75(2):871–875. doi: 10.1073/pnas.75.2.871. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Postlethwaite A. E., Snyderman R., Kang A. H. Generation of a fibroblast chemotactic factor in serum by activation of complement. J Clin Invest. 1979 Nov;64(5):1379–1385. doi: 10.1172/JCI109595. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Postlethwaite A. E., Snyderman R., Kang A. H. The chemotactic attraction of human fibroblasts to a lymphocyte-derived factor. J Exp Med. 1976 Nov 2;144(5):1188–1203. doi: 10.1084/jem.144.5.1188. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Senior R. M., Griffin G. L., Mecham R. P. Chemotactic responses of fibroblasts to tropoelastin and elastin-derived peptides. J Clin Invest. 1982 Sep;70(3):614–618. doi: 10.1172/JCI110654. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Seppä H. E., Yamada K. M., Seppä S. T., Silver M. H., Kleinman H. K., Schiffmann E. The cell binding fragment of fibronectin is chemotactic for fibroblasts. Cell Biol Int Rep. 1981 Aug;5(8):813–819. doi: 10.1016/0309-1651(81)90253-8. [DOI] [PubMed] [Google Scholar]
  22. 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]

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