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. 1994 Sep;49(9):867–871. doi: 10.1136/thx.49.9.867

Desensitisation of neutrophil responses by systemic interleukin 8 in cystic fibrosis.

Y Dai 1, T P Dean 1, M K Church 1, J O Warner 1, J K Shute 1
PMCID: PMC475175  PMID: 7940424

Abstract

BACKGROUND--Inflammation associated with neutrophil infiltration is a commonly observed feature of children with cystic fibrosis. Production of the major neutrophil chemotactic cytokine interleukin 8 (IL-8) is potentially of great importance in the pathology of cystic fibrosis. Concentrations of IL-8 in both sputum and bronchoalveolar lavage fluid have been found to be higher in children with cystic fibrosis than in controls. The IL-8 induced chemotactic response and numbers of IL-8 receptors on peripheral neutrophils obtained from children with cystic fibrosis have been compared with a control group of children. METHODS--Cells were isolated from 18 patients with cystic fibrosis (aged 4-20 years) and 13 controls (aged 5-12 years) by dextran centrifugation followed by separation on Lymphoprep. Chemotaxis was assayed using multiwell microchemotaxis chambers and 5 microns polycarbonate filters. Filters were fixed and stained with Haema-Gurr for counting. Results were expressed as numbers of neutrophils per high power field (HPF). RESULTS--At the optimum concentration (1 x 10(-8) mol/l) the number of cells migrating were similar for controls (150 (12)/HPF) and for the cystic fibrosis group (140 (14)/HPF)). At lower concentrations the numbers of neutrophils migrating were lower for the cystic fibrosis group. Scatchard analysis of 125I-labelled IL-8 binding revealed lower numbers of receptors on neutrophils from patients with cystic fibrosis (22,000 per cell) than from controls (75,000 per cell). CONCLUSIONS--Reduced responsiveness to IL-8 of neutrophils from patients with cystic fibrosis is associated with receptor desensitisation as a result of exposure to high systemic levels of IL-8.

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Selected References

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

  1. Anttila H. S., Reitamo S., Erkko P., Ceska M., Moser B., Baggiolini M. Interleukin-8 immunoreactivity in the skin of healthy subjects and patients with palmoplantar pustulosis and psoriasis. J Invest Dermatol. 1992 Jan;98(1):96–101. doi: 10.1111/1523-1747.ep12495817. [DOI] [PubMed] [Google Scholar]
  2. Arenberger P., Kemény L., Süss R., Michel G., Peter R. U., Ruzicka T. Interleukin-8 receptors in normal and psoriatic polymorphonuclear leukocytes. Acta Derm Venereol. 1992 Sep;72(5):334–336. [PubMed] [Google Scholar]
  3. Barker J. N., Griffiths C. E., Nickoloff B. J. NAP-1/IL-8 immunoreactivity in normal and psoriatic skin. J Invest Dermatol. 1991 Sep;97(3):606–608. doi: 10.1111/1523-1747.ep12481959. [DOI] [PubMed] [Google Scholar]
  4. Dean T. P., Dai Y., Shute J. K., Church M. K., Warner J. O. Interleukin-8 concentrations are elevated in bronchoalveolar lavage, sputum, and sera of children with cystic fibrosis. Pediatr Res. 1993 Aug;34(2):159–161. doi: 10.1203/00006450-199308000-00010. [DOI] [PubMed] [Google Scholar]
  5. Devreotes P. N., Zigmond S. H. Chemotaxis in eukaryotic cells: a focus on leukocytes and Dictyostelium. Annu Rev Cell Biol. 1988;4:649–686. doi: 10.1146/annurev.cb.04.110188.003245. [DOI] [PubMed] [Google Scholar]
  6. Grob P. M., David E., Warren T. C., DeLeon R. P., Farina P. R., Homon C. A. Characterization of a receptor for human monocyte-derived neutrophil chemotactic factor/interleukin-8. J Biol Chem. 1990 May 15;265(14):8311–8316. [PubMed] [Google Scholar]
  7. Kerem B., Rommens J. M., Buchanan J. A., Markiewicz D., Cox T. K., Chakravarti A., Buchwald M., Tsui L. C. Identification of the cystic fibrosis gene: genetic analysis. Science. 1989 Sep 8;245(4922):1073–1080. doi: 10.1126/science.2570460. [DOI] [PubMed] [Google Scholar]
  8. Kunkel S. L., Standiford T., Kasahara K., Strieter R. M. Interleukin-8 (IL-8): the major neutrophil chemotactic factor in the lung. Exp Lung Res. 1991 Jan-Feb;17(1):17–23. doi: 10.3109/01902149109063278. [DOI] [PubMed] [Google Scholar]
  9. Lawrence R. H., Sorrelli T. C. Decreased polymorphonuclear leucocyte chemotactic response to leukotriene B4 in cystic fibrosis. Clin Exp Immunol. 1992 Aug;89(2):321–324. doi: 10.1111/j.1365-2249.1992.tb06953.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Peichl P., Ceska M., Broell H., Effenberger F., Lindley I. J. Human neutrophil activating peptide/interleukin 8 acts as an autoantigen in rheumatoid arthritis. Ann Rheum Dis. 1992 Jan;51(1):19–22. doi: 10.1136/ard.51.1.19. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Rankin J. A., Sylvester I., Smith S., Yoshimura T., Leonard E. J. Macrophages cultured in vitro release leukotriene B4 and neutrophil attractant/activation protein (interleukin 8) sequentially in response to stimulation with lipopolysaccharide and zymosan. J Clin Invest. 1990 Nov;86(5):1556–1564. doi: 10.1172/JCI114875. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Rolfe M. W., Kunkel S. L., Standiford T. J., Chensue S. W., Allen R. M., Evanoff H. L., Phan S. H., Strieter R. M. Pulmonary fibroblast expression of interleukin-8: a model for alveolar macrophage-derived cytokine networking. Am J Respir Cell Mol Biol. 1991 Nov;5(5):493–501. doi: 10.1165/ajrcmb/5.5.493. [DOI] [PubMed] [Google Scholar]
  13. Samanta A. K., Oppenheim J. J., Matsushima K. Interleukin 8 (monocyte-derived neutrophil chemotactic factor) dynamically regulates its own receptor expression on human neutrophils. J Biol Chem. 1990 Jan 5;265(1):183–189. [PubMed] [Google Scholar]
  14. Schröder J. M., Christophers E. Secretion of novel and homologous neutrophil-activating peptides by LPS-stimulated human endothelial cells. J Immunol. 1989 Jan 1;142(1):244–251. [PubMed] [Google Scholar]
  15. Schröder J. M., Mrowietz U., Christophers E. Identification of different charged species of a human monocyte derived neutrophil activating peptide (MONAP). Biochem Biophys Res Commun. 1988 Apr 15;152(1):277–284. doi: 10.1016/s0006-291x(88)80711-3. [DOI] [PubMed] [Google Scholar]
  16. Schröder J. M., Mrowietz U., Christophers E. Purification and partial biologic characterization of a human lymphocyte-derived peptide with potent neutrophil-stimulating activity. J Immunol. 1988 May 15;140(10):3534–3540. [PubMed] [Google Scholar]
  17. 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]
  18. Sylvester I., Yoshimura T., Sticherling M., Schröder J. M., Ceska M., Peichl P., Leonard E. J. Neutrophil attractant protein-1-immunoglobulin G immune complexes and free anti-NAP-1 antibody in normal human serum. J Clin Invest. 1992 Aug;90(2):471–481. doi: 10.1172/JCI115883. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Sylvester I., Yoshimura T., Sticherling M., Schröder J. M., Ceska M., Peichl P., Leonard E. J. Neutrophil attractant protein-1-immunoglobulin G immune complexes and free anti-NAP-1 antibody in normal human serum. J Clin Invest. 1992 Aug;90(2):471–481. doi: 10.1172/JCI115883. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Warner J. O. Immunology of cystic fibrosis. Br Med Bull. 1992 Oct;48(4):893–911. doi: 10.1093/oxfordjournals.bmb.a072584. [DOI] [PubMed] [Google Scholar]

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