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. 1999 Nov;54(11):1015–1020. doi: 10.1136/thx.54.11.1015

Granulocyte-colony stimulating factor levels in bronchoalveolar lavage fluid from patients with idiopathic pulmonary fibrosis

J Ashitani 1, H Mukae 1, H Taniguchi 1, T Ihi 1, J Kadota 1, S Kohno 1, S Matsukura 1
PMCID: PMC1745399  PMID: 10525561

Abstract

BACKGROUND—Granulocyte-colony stimulating factor (G-CSF) is known as a potent neutrophil chemotactic glycoprotein in vitro but its contribution to chemotactic activity in neutrophil mediated lung diseases is not yet known. The aims of this study were to determine whether G-CSF is present in high concentrations in bronchoalveolar lavage (BAL) fluid of patients with idiopathic pulmonary fibrosis (IPF, also called cryptogenic fibrosing alveolitis), a neutrophil mediated lung disease, and to what extent G-CSF in BAL fluid contributes to neutrophil accumulation in the lung of patients with IPF.
METHODS—G-CSF concentrations in BAL fluid samples from 16 healthy volunteers, 24 patients with IPF, and 73 patients with non-IPF lung disease were measured by enzyme linked immunosorbent assay. The relationship between G-CSF concentrations and neutrophil count in BAL fluid was also examined. Neutrophil chemotactic activity (NCA) was measured in BAL fluid in healthy volunteers and patients with IPF. The contribution of G-CSF to overall NCA in lungs with IPF was assessed by repeating the measurement of NCA after a complete neutralisation of G-CSF bioactivity by anti-human G-CSF antiserum.
RESULTS—Detectable levels of G-CSF were found in BAL fluid of 83% of patients with IPF while the levels in all healthy volunteers were below the detection limit. In patients with IPF a significant correlation was observed between the BAL fluid neutrophil count and the concentration of G-CSF in the BAL fluid. The neutrophil count also correlated significantly with percentage forced vital capacity. In BAL fluid samples from patients with IPF the mean NCA value was reduced by 35% after neutralisation with an anti-human G-CSF antiserum.
CONCLUSIONS—G-CSF may be involved in enhancing neutrophil accumulation in the lungs of patients with IPF.



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Selected References

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  1. Car B. D., Meloni F., Luisetti M., Semenzato G., Gialdroni-Grassi G., Walz A. Elevated IL-8 and MCP-1 in the bronchoalveolar lavage fluid of patients with idiopathic pulmonary fibrosis and pulmonary sarcoidosis. Am J Respir Crit Care Med. 1994 Mar;149(3 Pt 1):655–659. doi: 10.1164/ajrccm.149.3.8118632. [DOI] [PubMed] [Google Scholar]
  2. Car B. D., Meloni F., Luisetti M., Semenzato G., Gialdroni-Grassi G., Walz A. Elevated IL-8 and MCP-1 in the bronchoalveolar lavage fluid of patients with idiopathic pulmonary fibrosis and pulmonary sarcoidosis. Am J Respir Crit Care Med. 1994 Mar;149(3 Pt 1):655–659. doi: 10.1164/ajrccm.149.3.8118632. [DOI] [PubMed] [Google Scholar]
  3. Carré P. C., Mortenson R. L., King T. E., Jr, Noble P. W., Sable C. L., Riches D. W. Increased expression of the interleukin-8 gene by alveolar macrophages in idiopathic pulmonary fibrosis. A potential mechanism for the recruitment and activation of neutrophils in lung fibrosis. J Clin Invest. 1991 Dec;88(6):1802–1810. doi: 10.1172/JCI115501. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cohen A. M., Zsebo K. M., Inoue H., Hines D., Boone T. C., Chazin V. R., Tsai L., Ritch T., Souza L. M. In vivo stimulation of granulopoiesis by recombinant human granulocyte colony-stimulating factor. Proc Natl Acad Sci U S A. 1987 Apr;84(8):2484–2488. doi: 10.1073/pnas.84.8.2484. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Crystal R. G., Gadek J. E., Ferrans V. J., Fulmer J. D., Line B. R., Hunninghake G. W. Interstitial lung disease: current concepts of pathogenesis, staging and therapy. Am J Med. 1981 Mar;70(3):542–568. doi: 10.1016/0002-9343(81)90577-5. [DOI] [PubMed] [Google Scholar]
  6. Falk W., Goodwin R. H., Jr, Leonard E. J. A 48-well micro chemotaxis assembly for rapid and accurate measurement of leukocyte migration. J Immunol Methods. 1980;33(3):239–247. doi: 10.1016/0022-1759(80)90211-2. [DOI] [PubMed] [Google Scholar]
  7. Ferrante A., Thong Y. H. A rapid one-step procedure for purification of mononuclear and polymorphonuclear leukocytes from human blood using a modification of the Hypaque-Ficoll technique. J Immunol Methods. 1978;24(3-4):389–393. doi: 10.1016/0022-1759(78)90143-6. [DOI] [PubMed] [Google Scholar]
  8. Gabrilove J. L., Jakubowski A., Scher H., Sternberg C., Wong G., Grous J., Yagoda A., Fain K., Moore M. A., Clarkson B. Effect of granulocyte colony-stimulating factor on neutropenia and associated morbidity due to chemotherapy for transitional-cell carcinoma of the urothelium. N Engl J Med. 1988 Jun 2;318(22):1414–1422. doi: 10.1056/NEJM198806023182202. [DOI] [PubMed] [Google Scholar]
  9. Gadek J. E., Hunninghake G. W., Zimmerman R. L., Crystal R. G. Regulation of the release of alveolar macrophage-derived neutrophil chemotactic factor. Am Rev Respir Dis. 1980 Apr;121(4):723–733. doi: 10.1164/arrd.1980.121.4.723. [DOI] [PubMed] [Google Scholar]
  10. Hällgren R., Bjermer L., Lundgren R., Venge P. The eosinophil component of the alveolitis in idiopathic pulmonary fibrosis. Signs of eosinophil activation in the lung are related to impaired lung function. Am Rev Respir Dis. 1989 Feb;139(2):373–377. doi: 10.1164/ajrccm/139.2.373. [DOI] [PubMed] [Google Scholar]
  11. Metcalf D. The molecular biology and functions of the granulocyte-macrophage colony-stimulating factors. Blood. 1986 Feb;67(2):257–267. [PubMed] [Google Scholar]
  12. Miller E. J., Cohen A. B., Nagao S., Griffith D., Maunder R. J., Martin T. R., Weiner-Kronish J. P., Sticherling M., Christophers E., Matthay M. A. Elevated levels of NAP-1/interleukin-8 are present in the airspaces of patients with the adult respiratory distress syndrome and are associated with increased mortality. Am Rev Respir Dis. 1992 Aug;146(2):427–432. doi: 10.1164/ajrccm/146.2.427. [DOI] [PubMed] [Google Scholar]
  13. Oishi K., Sonoda F., Kobayashi S., Iwagaki A., Nagatake T., Matsushima K., Matsumoto K. Role of interleukin-8 (IL-8) and an inhibitory effect of erythromycin on IL-8 release in the airways of patients with chronic airway diseases. Infect Immun. 1994 Oct;62(10):4145–4152. doi: 10.1128/iai.62.10.4145-4152.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Ozaki T., Hayashi H., Tani K., Ogushi F., Yasuoka S., Ogura T. Neutrophil chemotactic factors in the respiratory tract of patients with chronic airway diseases or idiopathic pulmonary fibrosis. Am Rev Respir Dis. 1992 Jan;145(1):85–91. doi: 10.1164/ajrccm/145.1.85. [DOI] [PubMed] [Google Scholar]
  15. Ozaki T., Hayashi H., Tani K., Ogushi F., Yasuoka S., Ogura T. Neutrophil chemotactic factors in the respiratory tract of patients with chronic airway diseases or idiopathic pulmonary fibrosis. Am Rev Respir Dis. 1992 Jan;145(1):85–91. doi: 10.1164/ajrccm/145.1.85. [DOI] [PubMed] [Google Scholar]
  16. Platzer E., Welte K., Gabrilove J. L., Lu L., Harris P., Mertelsmann R., Moore M. A. Biological activities of a human pluripotent hemopoietic colony stimulating factor on normal and leukemic cells. J Exp Med. 1985 Dec 1;162(6):1788–1801. doi: 10.1084/jem.162.6.1788. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Rudd R. M., Haslam P. L., Turner-Warwick M. Cryptogenic fibrosing alveolitis. Relationships of pulmonary physiology and bronchoalveolar lavage to response to treatment and prognosis. Am Rev Respir Dis. 1981 Jul;124(1):1–8. doi: 10.1164/arrd.1981.124.1.1. [DOI] [PubMed] [Google Scholar]
  18. Souza L. M., Boone T. C., Gabrilove J., Lai P. H., Zsebo K. M., Murdock D. C., Chazin V. R., Bruszewski J., Lu H., Chen K. K. Recombinant human granulocyte colony-stimulating factor: effects on normal and leukemic myeloid cells. Science. 1986 Apr 4;232(4746):61–65. doi: 10.1126/science.2420009. [DOI] [PubMed] [Google Scholar]
  19. Tazi A., Nioche S., Chastre J., Smiéjan J. M., Hance A. J. Spontaneous release of granulocyte colony-stimulating factor (G-CSF) by alveolar macrophages in the course of bacterial pneumonia and sarcoidosis: endotoxin-dependent and endotoxin-independent G-CSF release by cells recovered by bronchoalveolar lavage. Am J Respir Cell Mol Biol. 1991 Feb;4(2):140–147. doi: 10.1165/ajrcmb/4.2.140. [DOI] [PubMed] [Google Scholar]
  20. Technical recommendations and guidelines for bronchoalveolar lavage (BAL). Report of the European Society of Pneumology Task Group. Eur Respir J. 1989 Jun;2(6):561–585. [PubMed] [Google Scholar]
  21. Wang J. M., Chen Z. G., Colella S., Bonilla M. A., Welte K., Bordignon C., Mantovani A. Chemotactic activity of recombinant human granulocyte colony-stimulating factor. Blood. 1988 Nov;72(5):1456–1460. [PubMed] [Google Scholar]
  22. Watari K., Asano S., Shirafuji N., Kodo H., Ozawa K., Takaku F., Kamachi S. Serum granulocyte colony-stimulating factor levels in healthy volunteers and patients with various disorders as estimated by enzyme immunoassay. Blood. 1989 Jan;73(1):117–122. [PubMed] [Google Scholar]
  23. Wells A. U., Hansell D. M., Haslam P. L., Rubens M. B., Cailes J., Black C. M., du Bois R. M. Bronchoalveolar lavage cellularity: lone cryptogenic fibrosing alveolitis compared with the fibrosing alveolitis of systemic sclerosis. Am J Respir Crit Care Med. 1998 May;157(5 Pt 1):1474–1482. doi: 10.1164/ajrccm.157.5.9609096. [DOI] [PubMed] [Google Scholar]
  24. Wells A. U., Hansell D. M., Rubens M. B., Cullinan P., Haslam P. L., Black C. M., Du Bois R. M. Fibrosing alveolitis in systemic sclerosis. Bronchoalveolar lavage findings in relation to computed tomographic appearance. Am J Respir Crit Care Med. 1994 Aug;150(2):462–468. doi: 10.1164/ajrccm.150.2.8049830. [DOI] [PubMed] [Google Scholar]
  25. Welte K., Bonilla M. A., Gillio A. P., Boone T. C., Potter G. K., Gabrilove J. L., Moore M. A., O'Reilly R. J., Souza L. M. Recombinant human granulocyte colony-stimulating factor. Effects on hematopoiesis in normal and cyclophosphamide-treated primates. J Exp Med. 1987 Apr 1;165(4):941–948. doi: 10.1084/jem.165.4.941. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Xaubet A., Agustí C., Luburich P., Barberá J. A., Carrión M., Ayuso M. C., Roca J., Rodriguez-Roisin R. Interleukin-8 expression in bronchoalveolar lavage cells in the evaluation of alveolitis in idiopathic pulmonary fibrosis. Respir Med. 1998 Feb;92(2):338–344. doi: 10.1016/s0954-6111(98)90118-4. [DOI] [PubMed] [Google Scholar]
  27. Yong K. L., Linch D. C. Differential effects of granulocyte- and granulocyte-macrophage colony-stimulating factors (G- and GM-CSF) on neutrophil adhesion in vitro and in vivo. Eur J Haematol. 1992 Nov;49(5):251–259. doi: 10.1111/j.1600-0609.1992.tb00057.x. [DOI] [PubMed] [Google Scholar]

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