Skip to main content
NCBI home page
The American Journal of Pathology logoLink to The American Journal of Pathology
. 1993 Jul;143(1):130–142.

Sequential Expression of Transforming Growth Factors α and β1 by Eosinophils During Cutaneous Wound Healing in the Hamster

David T W Wong, R Bruce Donoff, James Yang, Bai-Zheng Song, Karekine Matossian, Naoyoshi Nagura, Aram Elovic, Jim McBride, George Gallagher, Randy Todd, Tao Chiang, Lin S-S Chou, Chou Ming Yung, Stephen J Galli, Peter F Weller
PMCID: PMC1886938  PMID: 8317544

Abstract

Transforming growth factor-α (TGF-α) and TGF-β1 have been proposed as important regulators of processes critical to successful wound healing. Although various cells present in wounds represent potential sources of either TGF-α and/or TGF-β, including macrophages, neutrophils, keratinocytes, fibroblasts, and endothelial cells, we recently identified eosinophils as an additional potential source of these cytokines. We therefore used in situ hybridization and immunohistochemistry to determine whether eosinophils represent significant sources of TGF-α and/or TGF-β1 in skin wounds in the hamster. We found that these wounds developed a prominent infiltration of eosinophils, and that eosinophils were a cellular source of both TGF-α and TGF-β1, mRNAs. TGF-α and TGF-β1 proteins were detectable both within eosinophils and extracellularly. Moreover, there was a sequential pattern of TGF-α and TGF-β1 expression by infiltrating eosinophils, with the onset of eosinophil-associated TGF-α expression preceding that of TGF-β1. This sequential pattern of TGF expression suggests that eosinophils may help to regulate critical biological processes during wound healing.

Full text

PDF
130

Images in this article

137Figure 4
on p.137
139Figure 6
on p.139
140Figure 7
on p.140

Selected References

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

  1. Barnard J. A., Lyons R. M., Moses H. L. The cell biology of transforming growth factor beta. Biochim Biophys Acta. 1990 Jun 1;1032(1):79–87. doi: 10.1016/0304-419x(90)90013-q. [DOI] [PubMed] [Google Scholar]
  2. Barrandon Y., Green H. Cell migration is essential for sustained growth of keratinocyte colonies: the roles of transforming growth factor-alpha and epidermal growth factor. Cell. 1987 Sep 25;50(7):1131–1137. doi: 10.1016/0092-8674(87)90179-6. [DOI] [PubMed] [Google Scholar]
  3. Bassett E. G., Baker J. R., BAKER P. A., MYERS D. B. Comparison of collagenase activity in eosinophil and neutrophil fractions from rat peritoneal exudates. Aust J Exp Biol Med Sci. 1976 Oct;54(5):459–465. doi: 10.1038/icb.1976.46. [DOI] [PubMed] [Google Scholar]
  4. Bassett E. G., Baker J. R., de Souza P. A light microscopical study of healing incised dermal wounds in rats, with special reference to eosinophil leucocytes and to the collagenous fibres of the periwound areas. Br J Exp Pathol. 1977 Dec;58(6):581–605. [PMC free article] [PubMed] [Google Scholar]
  5. Blasband A. J., Rogers K. T., Chen X. R., Azizkhan J. C., Lee D. C. Characterization of the rat transforming growth factor alpha gene and identification of promoter sequences. Mol Cell Biol. 1990 May;10(5):2111–2121. doi: 10.1128/mcb.10.5.2111. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Chiang T., McBride J., Chou M. Y., Nishimura I., Wong D. T. Molecular cloning of the complementary DNA encoding for the hamster TGF-alpha mature peptide. Carcinogenesis. 1991 Mar;12(3):529–532. doi: 10.1093/carcin/12.3.529. [DOI] [PubMed] [Google Scholar]
  7. Derynck R., Jarrett J. A., Chen E. Y., Eaton D. H., Bell J. R., Assoian R. K., Roberts A. B., Sporn M. B., Goeddel D. V. Human transforming growth factor-beta complementary DNA sequence and expression in normal and transformed cells. Nature. 1985 Aug 22;316(6030):701–705. doi: 10.1038/316701a0. [DOI] [PubMed] [Google Scholar]
  8. Derynck R., Roberts A. B., Winkler M. E., Chen E. Y., Goeddel D. V. Human transforming growth factor-alpha: precursor structure and expression in E. coli. Cell. 1984 Aug;38(1):287–297. doi: 10.1016/0092-8674(84)90550-6. [DOI] [PubMed] [Google Scholar]
  9. Elovic A., Galli S. J., Weller P. F., Chang A. L., Chiang T., Chou M. Y., Donoff R. B., Gallagher G. T., Matossian K., McBride J. Production of transforming growth factor alpha by hamster eosinophils. Am J Pathol. 1990 Dec;137(6):1425–1434. [PMC free article] [PubMed] [Google Scholar]
  10. Ffrench-Constant C., Van de Water L., Dvorak H. F., Hynes R. O. Reappearance of an embryonic pattern of fibronectin splicing during wound healing in the adult rat. J Cell Biol. 1989 Aug;109(2):903–914. doi: 10.1083/jcb.109.2.903. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Jakowlew S. B., Kondaiah P., Dillard P. J., Sporn M. B., Roberts A. B. A novel low molecular weight ribonucleic acid (RNA) related to transforming growth factor alpha messenger RNA. Mol Endocrinol. 1988 Nov;2(11):1056–1063. doi: 10.1210/mend-2-11-1056. [DOI] [PubMed] [Google Scholar]
  12. LEVENSON S. M., GEEVER E. F., CROWLEY L. V., OATES J. F., 3rd, BERARD C. W., ROSEN H. THE HEALING OF RAT SKIN WOUNDS. Ann Surg. 1965 Feb;161:293–308. doi: 10.1097/00000658-196502000-00019. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. McCrone E. L., Lucey D. R., Weller P. F. Fluorescent staining for leukocyte chemotaxis. Eosinophil-specific fluorescence with aniline blue. J Immunol Methods. 1988 Nov 10;114(1-2):79–88. doi: 10.1016/0022-1759(88)90157-3. [DOI] [PubMed] [Google Scholar]
  14. Nickoloff B. J., Karabin G. D., Barker J. N., Griffiths C. E., Sarma V., Mitra R. S., Elder J. T., Kunkel S. L., Dixit V. M. Cellular localization of interleukin-8 and its inducer, tumor necrosis factor-alpha in psoriasis. Am J Pathol. 1991 Jan;138(1):129–140. [PMC free article] [PubMed] [Google Scholar]
  15. Odukoya O., Schwartz J., Weichselbaum R., Shklar G. An epidermoid carcinoma cell line derived from hamster 7,12-dimethylbenz[a]anthracene-induced buccal pouch tumors. J Natl Cancer Inst. 1983 Dec;71(6):1253–1264. [PubMed] [Google Scholar]
  16. Ohno I., Lea R. G., Flanders K. C., Clark D. A., Banwatt D., Dolovich J., Denburg J., Harley C. B., Gauldie J., Jordana M. Eosinophils in chronically inflamed human upper airway tissues express transforming growth factor beta 1 gene (TGF beta 1). J Clin Invest. 1992 May;89(5):1662–1668. doi: 10.1172/JCI115764. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Ordman L. J., Gillman T. Studies in the healing of cutaneous wounds. I. The healing of incisions through the skin of pigs. Arch Surg. 1966 Dec;93(6):857–882. doi: 10.1001/archsurg.1966.01330060001001. [DOI] [PubMed] [Google Scholar]
  18. Pierce G. F., Mustoe T. A., Lingelbach J., Masakowski V. R., Griffin G. L., Senior R. M., Deuel T. F. Platelet-derived growth factor and transforming growth factor-beta enhance tissue repair activities by unique mechanisms. J Cell Biol. 1989 Jul;109(1):429–440. doi: 10.1083/jcb.109.1.429. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Pikaart M. J., Villeponteau B. Suppression of PCR amplification by high levels of RNA. Biotechniques. 1993 Jan;14(1):24–25. [PubMed] [Google Scholar]
  20. Quaglino D., Jr, Nanney L. B., Kennedy R., Davidson J. M. Transforming growth factor-beta stimulates wound healing and modulates extracellular matrix gene expression in pig skin. I. Excisional wound model. Lab Invest. 1990 Sep;63(3):307–319. [PubMed] [Google Scholar]
  21. Schreiber A. B., Winkler M. E., Derynck R. Transforming growth factor-alpha: a more potent angiogenic mediator than epidermal growth factor. Science. 1986 Jun 6;232(4755):1250–1253. doi: 10.1126/science.2422759. [DOI] [PubMed] [Google Scholar]
  22. Shull M. M., Ormsby I., Kier A. B., Pawlowski S., Diebold R. J., Yin M., Allen R., Sidman C., Proetzel G., Calvin D. Targeted disruption of the mouse transforming growth factor-beta 1 gene results in multifocal inflammatory disease. Nature. 1992 Oct 22;359(6397):693–699. doi: 10.1038/359693a0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Steele R. H., Wilhelm D. L. The inflammatory reaction in chemical injury. 3. Leucocytosis and other histological changes induced by superficial injury. Br J Exp Pathol. 1970 Jun;51(3):265–279. [PMC free article] [PubMed] [Google Scholar]
  24. Todd R., Donoff B. R., Chiang T., Chou M. Y., Elovic A., Gallagher G. T., Wong D. T. The eosinophil as a cellular source of transforming growth factor alpha in healing cutaneous wounds. Am J Pathol. 1991 Jun;138(6):1307–1313. [PMC free article] [PubMed] [Google Scholar]
  25. Wong D. T., Elovic A., Matossian K., Nagura N., McBride J., Chou M. Y., Gordon J. R., Rand T. H., Galli S. J., Weller P. F. Eosinophils from patients with blood eosinophilia express transforming growth factor beta 1. Blood. 1991 Nov 15;78(10):2702–2707. [PubMed] [Google Scholar]
  26. Wong D. T., Weller P. F., Galli S. J., Elovic A., Rand T. H., Gallagher G. T., Chiang T., Chou M. Y., Matossian K., McBride J. Human eosinophils express transforming growth factor alpha. J Exp Med. 1990 Sep 1;172(3):673–681. doi: 10.1084/jem.172.3.673. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The American Journal of Pathology are provided here courtesy of American Society for Investigative Pathology

RESOURCES