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. 1991 Sep;88(3):1048–1053. doi: 10.1172/JCI115366

Endobronchial allergen challenge in asthma. Demonstration of cellular source of granulocyte macrophage colony-stimulating factor by in situ hybridization.

D H Broide 1, G S Firestein 1
PMCID: PMC295519  PMID: 1885766

Abstract

Airway inflammation is thought to play an important role in the pathogenesis of asthma. We have used in situ hybridization and an immunoassay to determine whether granulocyte macrophage colony-stimulating factor (GM-CSF) (a cytokine capable of eosinophil activation) is present in the airway of asthmatics (n = 6) who have 37.0 +/- 15.1% airway eosinophilia after endobronchial allergen challenge. Levels of immunoreactive GM-CSF (less than 4 pg/ml pre-allergen versus 180.5 +/- 46.9 pg/ml post-allergen) increased significantly 24 h after endobronchial allergen stimulation. The cellular source of bronchoalveolar lavage (BAL) GM-CSF, as determined by in situ hybridization and immunoperoxidase staining, was derived predominantly from UCHL-1 positive BAL lymphocytes, as well as from a smaller population of alveolar macrophages. Before local endobronchial allergen challenge, less than 1% of lymphocytes and alveolar macrophages recovered by BAL expressed GM-CSF mRNA, whereas after allergen stimulation 92.6 +/- 3.4% of lymphocytes and 17.5 +/- 22.7% of alveolar macrophages expressed GM-CSF mRNA. This study provides evidence that in an experimental model of allergen-induced asthma, activation of the immune and inflammatory response (BAL lymphocyte and alveolar macrophage production of GM-CSF) is temporally associated with an inflammatory cell influx of eosinophils into the airway.

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Selected References

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

  1. Alvaro-Gracia J. M., Zvaifler N. J., Brown C. B., Kaushansky K., Firestein G. S. Cytokines in chronic inflammatory arthritis. VI. Analysis of the synovial cells involved in granulocyte-macrophage colony-stimulating factor production and gene expression in rheumatoid arthritis and its regulation by IL-1 and tumor necrosis factor-alpha. J Immunol. 1991 May 15;146(10):3365–3371. [PubMed] [Google Scholar]
  2. Casale T. B., Wood D., Richerson H. B., Zehr B., Zavala D., Hunninghake G. W. Direct evidence of a role for mast cells in the pathogenesis of antigen-induced bronchoconstriction. J Clin Invest. 1987 Nov;80(5):1507–1511. doi: 10.1172/JCI113234. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Chai H., Farr R. S., Froehlich L. A., Mathison D. A., McLean J. A., Rosenthal R. R., Sheffer A. L., Spector S. L., Townley R. G. Standardization of bronchial inhalation challenge procedures. J Allergy Clin Immunol. 1975 Oct;56(4):323–327. doi: 10.1016/0091-6749(75)90107-4. [DOI] [PubMed] [Google Scholar]
  4. Chan J. Y., Slamon D. J., Nimer S. D., Golde D. W., Gasson J. C. Regulation of expression of human granulocyte/macrophage colony-stimulating factor. Proc Natl Acad Sci U S A. 1986 Nov;83(22):8669–8673. doi: 10.1073/pnas.83.22.8669. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Corrigan C. J., Kay A. B. CD4 T-lymphocyte activation in acute severe asthma. Relationship to disease severity and atopic status. Am Rev Respir Dis. 1990 Apr;141(4 Pt 1):970–977. doi: 10.1164/ajrccm/141.4_Pt_1.. [DOI] [PubMed] [Google Scholar]
  6. Djukanović R., Roche W. R., Wilson J. W., Beasley C. R., Twentyman O. P., Howarth R. H., Holgate S. T. Mucosal inflammation in asthma. Am Rev Respir Dis. 1990 Aug;142(2):434–457. doi: 10.1164/ajrccm/142.2.434. [DOI] [PubMed] [Google Scholar]
  7. Firestein G. S., Alvaro-Gracia J. M., Maki R., Alvaro-Garcia J. M. Quantitative analysis of cytokine gene expression in rheumatoid arthritis. J Immunol. 1990 May 1;144(9):3347–3353. [PubMed] [Google Scholar]
  8. Gerblich A. A., Campbell A. E., Schuyler M. R. Changes in T-lymphocyte subpopulations after antigenic bronchial provocation in asthmatics. N Engl J Med. 1984 May 24;310(21):1349–1352. doi: 10.1056/NEJM198405243102103. [DOI] [PubMed] [Google Scholar]
  9. Gleich G. J. The eosinophil and bronchial asthma: current understanding. J Allergy Clin Immunol. 1990 Feb;85(2):422–436. doi: 10.1016/0091-6749(90)90151-s. [DOI] [PubMed] [Google Scholar]
  10. Howell C. J., Pujol J. L., Crea A. E., Davidson R., Gearing A. J., Godard P., Lee T. H. Identification of an alveolar macrophage-derived activity in bronchial asthma that enhances leukotriene C4 generation by human eosinophils stimulated by ionophore A23187 as a granulocyte-macrophage colony-stimulating factor. Am Rev Respir Dis. 1989 Nov;140(5):1340–1347. doi: 10.1164/ajrccm/140.5.1340. [DOI] [PubMed] [Google Scholar]
  11. Lopez A. F., Sanderson C. J., Gamble J. R., Campbell H. D., Young I. G., Vadas M. A. Recombinant human interleukin 5 is a selective activator of human eosinophil function. J Exp Med. 1988 Jan 1;167(1):219–224. doi: 10.1084/jem.167.1.219. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Metzger W. J., Richerson H. B., Worden K., Monick M., Hunninghake G. W. Bronchoalveolar lavage of allergic asthmatic patients following allergen bronchoprovocation. Chest. 1986 Apr;89(4):477–483. doi: 10.1378/chest.89.4.477. [DOI] [PubMed] [Google Scholar]
  13. Owen W. F., Jr, Rothenberg M. E., Silberstein D. S., Gasson J. C., Stevens R. L., Austen K. F., Soberman R. J. Regulation of human eosinophil viability, density, and function by granulocyte/macrophage colony-stimulating factor in the presence of 3T3 fibroblasts. J Exp Med. 1987 Jul 1;166(1):129–141. doi: 10.1084/jem.166.1.129. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Rothenberg M. E., Owen W. F., Jr, Silberstein D. S., Woods J., Soberman R. J., Austen K. F., Stevens R. L. Human eosinophils have prolonged survival, enhanced functional properties, and become hypodense when exposed to human interleukin 3. J Clin Invest. 1988 Jun;81(6):1986–1992. doi: 10.1172/JCI113547. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Silberstein D. S., David J. R. Tumor necrosis factor enhances eosinophil toxicity to Schistosoma mansoni larvae. Proc Natl Acad Sci U S A. 1986 Feb;83(4):1055–1059. doi: 10.1073/pnas.83.4.1055. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Silberstein D. S., Owen W. F., Gasson J. C., DiPersio J. F., Golde D. W., Bina J. C., Soberman R., Austen K. F., David J. R. Enhancement of human eosinophil cytotoxicity and leukotriene synthesis by biosynthetic (recombinant) granulocyte-macrophage colony-stimulating factor. J Immunol. 1986 Nov 15;137(10):3290–3294. [PubMed] [Google Scholar]
  17. Terry L. A., Brown M. H., Beverley P. C. The monoclonal antibody, UCHL1, recognizes a 180,000 MW component of the human leucocyte-common antigen, CD45. Immunology. 1988 Jun;64(2):331–336. [PMC free article] [PubMed] [Google Scholar]

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