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The American Journal of Pathology logoLink to The American Journal of Pathology
. 1993 May;142(5):1423–1431.

Enhanced production of the chemotactic cytokines interleukin-8 and monocyte chemoattractant protein-1 in human abdominal aortic aneurysms.

A E Koch 1, S L Kunkel 1, W H Pearce 1, M R Shah 1, D Parikh 1, H L Evanoff 1, G K Haines 1, M D Burdick 1, R M Strieter 1
PMCID: PMC1886921  PMID: 8494046

Abstract

Inflammatory leukocytes play a central role in the pathogenesis of human atherosclerotic disease, from early atherogenesis to the late stages of atherosclerosis, such as aneurysm formation. We have shown previously that human abdominal aortic aneurysms are characterized by the presence of numerous chronic inflammatory cells throughout the vessel wall (Am J Pathol 1990, 137: 1199-1213). The signals that attract lymphocytes and monocytes into the aortic wall in aneurysmal disease remain to be precisely defined. We have studied the production of the chemotactic cytokines interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) by aortic tissues obtained from 47 subjects. We compared the antigenic production of these cytokines by explants of: 1) human abdominal aneurysmal tissue, 2) occlusive (atherosclerotic) aortas, and 3) normal aortas. IL-8, which is chemotactic for neutrophils, lymphocytes, and endothelial cells was liberated in greater quantities by abdominal aortic aneurysms than by occlusive or normal aortas. Using immunohistochemistry, macrophages, and to a lesser degree endothelial cells, were found to be positive for the expression of antigenic IL-8. Similarly, MCP-1, a potent chemotactic cytokine for monocytes/macrophages, was released by explants from abdominal aortic aneurysms in greater quantities than by explants from occlusive or normal aortas. Using immunohistochemistry, the predominant MCP-1 antigen-positive cells were macrophages and to a lesser extent smooth muscle cells. Our results indicate that human abdominal aortic aneurysms produce IL-8 and MCP-1, both of which may serve to recruit additional inflammatory cells into the abdominal aortic wall, hence perpetuating the inflammatory reaction that may result in the pathology of vessel wall destruction and aortic aneurysm formation.

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Selected References

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  1. Baggiolini M., Walz A., Kunkel S. L. Neutrophil-activating peptide-1/interleukin 8, a novel cytokine that activates neutrophils. J Clin Invest. 1989 Oct;84(4):1045–1049. doi: 10.1172/JCI114265. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Cushing S. D., Berliner J. A., Valente A. J., Territo M. C., Navab M., Parhami F., Gerrity R., Schwartz C. J., Fogelman A. M. Minimally modified low density lipoprotein induces monocyte chemotactic protein 1 in human endothelial cells and smooth muscle cells. Proc Natl Acad Sci U S A. 1990 Jul;87(13):5134–5138. doi: 10.1073/pnas.87.13.5134. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Evanoff H. L., Burdick M. D., Moore S. A., Kunkel S. L., Strieter R. M. A sensitive ELISA for the detection of human monocyte chemoattractant protein-1 (MCP-1). Immunol Invest. 1992 Feb;21(1):39–45. doi: 10.3109/08820139209069361. [DOI] [PubMed] [Google Scholar]
  4. Furutani Y., Nomura H., Notake M., Oyamada Y., Fukui T., Yamada M., Larsen C. G., Oppenheim J. J., Matsushima K. Cloning and sequencing of the cDNA for human monocyte chemotactic and activating factor (MCAF). Biochem Biophys Res Commun. 1989 Feb 28;159(1):249–255. doi: 10.1016/0006-291x(89)92430-3. [DOI] [PubMed] [Google Scholar]
  5. Hansson G. K., Jonasson L., Seifert P. S., Stemme S. Immune mechanisms in atherosclerosis. Arteriosclerosis. 1989 Sep-Oct;9(5):567–578. doi: 10.1161/01.atv.9.5.567. [DOI] [PubMed] [Google Scholar]
  6. Hsu S. M., Raine L., Fanger H. Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochem. 1981 Apr;29(4):577–580. doi: 10.1177/29.4.6166661. [DOI] [PubMed] [Google Scholar]
  7. Koch A. E., Burrows J. C., Haines G. K., Carlos T. M., Harlan J. M., Leibovich S. J. Immunolocalization of endothelial and leukocyte adhesion molecules in human rheumatoid and osteoarthritic synovial tissues. Lab Invest. 1991 Mar;64(3):313–320. [PubMed] [Google Scholar]
  8. Koch A. E., Burrows J. C., Skoutelis A., Marder R., Domer P. H., Anderson B., Leibovich S. J. Monoclonal antibodies detect monocyte/macrophage activation and differentiation antigens and identify functionally distinct subpopulations of human rheumatoid synovial tissue macrophages. Am J Pathol. 1991 Jan;138(1):165–173. [PMC free article] [PubMed] [Google Scholar]
  9. Koch A. E., Haines G. K., Rizzo R. J., Radosevich J. A., Pope R. M., Robinson P. G., Pearce W. H. Human abdominal aortic aneurysms. Immunophenotypic analysis suggesting an immune-mediated response. Am J Pathol. 1990 Nov;137(5):1199–1213. [PMC free article] [PubMed] [Google Scholar]
  10. Koch A. E., Kunkel S. L., Burrows J. C., Evanoff H. L., Haines G. K., Pope R. M., Strieter R. M. Synovial tissue macrophage as a source of the chemotactic cytokine IL-8. J Immunol. 1991 Oct 1;147(7):2187–2195. [PubMed] [Google Scholar]
  11. Koch A. E., Polverini P. J., Kunkel S. L., Harlow L. A., DiPietro L. A., Elner V. M., Elner S. G., Strieter R. M. Interleukin-8 as a macrophage-derived mediator of angiogenesis. Science. 1992 Dec 11;258(5089):1798–1801. doi: 10.1126/science.1281554. [DOI] [PubMed] [Google Scholar]
  12. Koch A. E., Robinson P. G., Radosevich J. A., Pope R. M. Distribution of CD45RA and CD45RO T-lymphocyte subsets in rheumatoid arthritis synovial tissue. J Clin Immunol. 1990 Jul;10(4):192–199. doi: 10.1007/BF00918651. [DOI] [PubMed] [Google Scholar]
  13. Larsen C. G., Anderson A. O., Appella E., Oppenheim J. J., Matsushima K. The neutrophil-activating protein (NAP-1) is also chemotactic for T lymphocytes. Science. 1989 Mar 17;243(4897):1464–1466. doi: 10.1126/science.2648569. [DOI] [PubMed] [Google Scholar]
  14. Loppnow H., Libby P. Proliferating or interleukin 1-activated human vascular smooth muscle cells secrete copious interleukin 6. J Clin Invest. 1990 Mar;85(3):731–738. doi: 10.1172/JCI114498. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Matsushima K., Morishita K., Yoshimura T., Lavu S., Kobayashi Y., Lew W., Appella E., Kung H. F., Leonard E. J., Oppenheim J. J. Molecular cloning of a human monocyte-derived neutrophil chemotactic factor (MDNCF) and the induction of MDNCF mRNA by interleukin 1 and tumor necrosis factor. J Exp Med. 1988 Jun 1;167(6):1883–1893. doi: 10.1084/jem.167.6.1883. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Matsushima K., Oppenheim J. J. Interleukin 8 and MCAF: novel inflammatory cytokines inducible by IL 1 and TNF. Cytokine. 1989 Nov;1(1):2–13. doi: 10.1016/1043-4666(89)91043-0. [DOI] [PubMed] [Google Scholar]
  17. Navab M., Imes S. S., Hama S. Y., Hough G. P., Ross L. A., Bork R. W., Valente A. J., Berliner J. A., Drinkwater D. C., Laks H. Monocyte transmigration induced by modification of low density lipoprotein in cocultures of human aortic wall cells is due to induction of monocyte chemotactic protein 1 synthesis and is abolished by high density lipoprotein. J Clin Invest. 1991 Dec;88(6):2039–2046. doi: 10.1172/JCI115532. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Nelken N. A., Coughlin S. R., Gordon D., Wilcox J. N. Monocyte chemoattractant protein-1 in human atheromatous plaques. J Clin Invest. 1991 Oct;88(4):1121–1127. doi: 10.1172/JCI115411. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Norris D. A., Clark R. A., Swigart L. M., Huff J. C., Weston W. L., Howell S. E. Fibronectin fragment(s) are chemotactic for human peripheral blood monocytes. J Immunol. 1982 Oct;129(4):1612–1618. [PubMed] [Google Scholar]
  20. Peveri P., Walz A., Dewald B., Baggiolini M. A novel neutrophil-activating factor produced by human mononuclear phagocytes. J Exp Med. 1988 May 1;167(5):1547–1559. doi: 10.1084/jem.167.5.1547. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Pope R. M., Landay A., Modlin R. L., Lessard J., Koch A. E. Gamma/delta T cell receptor positive T cells in the inflammatory joint: lack of association with response to soluble antigens. Cell Immunol. 1991 Oct 1;137(1):127–138. doi: 10.1016/0008-8749(91)90063-h. [DOI] [PubMed] [Google Scholar]
  22. Postlethwaite A. E., Kang A. H. Collagen-and collagen peptide-induced chemotaxis of human blood monocytes. J Exp Med. 1976 Jun 1;143(6):1299–1307. doi: 10.1084/jem.143.6.1299. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Poston R. N., Haskard D. O., Coucher J. R., Gall N. P., Johnson-Tidey R. R. Expression of intercellular adhesion molecule-1 in atherosclerotic plaques. Am J Pathol. 1992 Mar;140(3):665–673. [PMC free article] [PubMed] [Google Scholar]
  24. Rollins B. J., Stier P., Ernst T., Wong G. G. The human homolog of the JE gene encodes a monocyte secretory protein. Mol Cell Biol. 1989 Nov;9(11):4687–4695. doi: 10.1128/mcb.9.11.4687. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Senior R. M., Griffin G. L., Mecham R. P. Chemotactic activity of elastin-derived peptides. J Clin Invest. 1980 Oct;66(4):859–862. doi: 10.1172/JCI109926. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Standiford T. J., Kunkel S. L., Basha M. A., Chensue S. W., Lynch J. P., 3rd, Toews G. B., Westwick J., Strieter R. M. Interleukin-8 gene expression by a pulmonary epithelial cell line. A model for cytokine networks in the lung. J Clin Invest. 1990 Dec;86(6):1945–1953. doi: 10.1172/JCI114928. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Stella A., Gargiulo M., Pasquinelli G., Preda P., Faggioli G. L., Cenacchi G., D'Addato M. The cellular component in the parietal infiltrate of inflammatory abdominal aortic aneurysms (IAAA). Eur J Vasc Surg. 1991 Feb;5(1):65–70. doi: 10.1016/s0950-821x(05)80929-6. [DOI] [PubMed] [Google Scholar]
  28. Strieter R. M., Chensue S. W., Basha M. A., Standiford T. J., Lynch J. P., Baggiolini M., Kunkel S. L. Human alveolar macrophage gene expression of interleukin-8 by tumor necrosis factor-alpha, lipopolysaccharide, and interleukin-1 beta. Am J Respir Cell Mol Biol. 1990 Apr;2(4):321–326. doi: 10.1165/ajrcmb/2.4.321. [DOI] [PubMed] [Google Scholar]
  29. Strieter R. M., Kunkel S. L., Elner V. M., Martonyi C. L., Koch A. E., Polverini P. J., Elner S. G. Interleukin-8. A corneal factor that induces neovascularization. Am J Pathol. 1992 Dec;141(6):1279–1284. [PMC free article] [PubMed] [Google Scholar]
  30. Strieter R. M., Kunkel S. L., Showell H. J., Remick D. G., Phan S. H., Ward P. A., Marks R. M. Endothelial cell gene expression of a neutrophil chemotactic factor by TNF-alpha, LPS, and IL-1 beta. Science. 1989 Mar 17;243(4897):1467–1469. doi: 10.1126/science.2648570. [DOI] [PubMed] [Google Scholar]
  31. Sueishi K., Yasunaga C., Castellanos E., Kumamoto M., Tanaka K. Sustained arterial injury and progression of atherosclerosis. Ann N Y Acad Sci. 1990;598:223–231. doi: 10.1111/j.1749-6632.1990.tb42294.x. [DOI] [PubMed] [Google Scholar]
  32. Wahl S. M., Hunt D. A., Wakefield L. M., McCartney-Francis N., Wahl L. M., Roberts A. B., Sporn M. B. Transforming growth factor type beta induces monocyte chemotaxis and growth factor production. Proc Natl Acad Sci U S A. 1987 Aug;84(16):5788–5792. doi: 10.1073/pnas.84.16.5788. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Wang J. M., Sica A., Peri G., Walter S., Padura I. M., Libby P., Ceska M., Lindley I., Colotta F., Mantovani A. Expression of monocyte chemotactic protein and interleukin-8 by cytokine-activated human vascular smooth muscle cells. Arterioscler Thromb. 1991 Sep-Oct;11(5):1166–1174. doi: 10.1161/01.atv.11.5.1166. [DOI] [PubMed] [Google Scholar]
  34. Yoshimura T., Robinson E. A., Tanaka S., Appella E., Kuratsu J., Leonard E. J. Purification and amino acid analysis of two human glioma-derived monocyte chemoattractants. J Exp Med. 1989 Apr 1;169(4):1449–1459. doi: 10.1084/jem.169.4.1449. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Yoshimura T., Robinson E. A., Tanaka S., Appella E., Leonard E. J. Purification and amino acid analysis of two human monocyte chemoattractants produced by phytohemagglutinin-stimulated human blood mononuclear leukocytes. J Immunol. 1989 Mar 15;142(6):1956–1962. [PubMed] [Google Scholar]

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