Cell cultures from bronchial subepithelial myofibroblasts enhance eosinophil survival in vitro

Mechanisms of eosinophil accumulation and activation in the bronchial mucosa are crucial for the pathogenesis of asthma. The location of specialized fibroblasts, myofibroblasts, beneath the bronchial basement membrane and their proximity to infiltrating eosinophils potentially enable the myofibroblasts to modulate eosinophil survival and function in asthma. The aim of this study was to investigate the effects of bronchial myofibroblasts on eosinophil survival in vitro. Eosinophils from human peripheral blood were exposed to cell cultures from bronchial myofibroblasts and to myofibroblast-conditioned media. Eosinophil viability was assessed and granulocyte/macrophage colony-stimulating factor (GM-CSF) production was examined in co-culture supernatants and as messenger ribonucleic acid (mRNA) in myofibroblasts. Eosinophil survival was significantly increased and eosinophil apoptosis was inhibited by co-culture with myofibroblasts. Conditioned medium from tumour necrosis factor-alpha (TNF-alpha)-stimulated myofibroblasts also prolonged eosinophil survival. This effect could be blocked by GM-CSF antibody. GM-CSF mRNA and secretion from myofibroblasts were increased in co-cultures and by eosinophil-conditioned medium. Addition of antibodies to TNF-alpha and interleukin-1 alpha (IL-1 alpha) to co-cultures resulted in significant reduction both in eosinophil survival and GM-CSF levels. Blocking of fibronectin in the co-cultures did not affect the eosinophil survival enhancing activity. Prednisolone inhibited the eosinophil survival enhancing activity of the co-cultures by suppression of GM-CSF production. Soluble eosinophil-derived cytokines are involved in the interaction of eosinophils with myofibroblasts, which results in a tumour necrosis factor-alpha/interleukin-1 alpha mediated release of granulocyte/macrophage colony-stimulating factor from myofibroblasts. Bronchial myofibroblasts can, thereby, contribute to allergic inflammation by granulocyte/macrophage colony-stimulating factor-mediated inhibition of eosinophil apoptosis.

This article has been cited by other articles:

				J. E. Ward, T. Harris, T. Bamford, A. Mast, M. C. F. Pain, C. Robertson, D. Smallwood, T. Tran, J. Wilson, and A. G. Stewart Proliferation is not increased in airway myofibroblasts isolated from asthmatics Eur. Respir. J., August 1, 2008; 32(2): 362 - 371. [Abstract] [Full Text] [PDF]

				V. Dolgachev, A. A. Berlin, and N. W. Lukacs Eosinophil Activation of Fibroblasts from Chronic Allergen-Induced Disease Utilizes Stem Cell Factor for Phenotypic Changes Am. J. Pathol., January 1, 2008; 172(1): 68 - 76. [Abstract] [Full Text] [PDF]

				L-P. Boulet and P. J. Sterk A new series on airway remodelling Eur. Respir. J., February 1, 2007; 29(2): 231 - 232. [Full Text] [PDF]

				J. Y. Cho, M. Miller, K. J. Baek, J. W. Han, J. Nayar, M. Rodriguez, S. Y. Lee, K. McElwain, S. McElwain, E. Raz, et al. Immunostimulatory DNA Inhibits Transforming Growth Factor-{beta} Expression and Airway Remodeling Am. J. Respir. Cell Mol. Biol., May 1, 2004; 30(5): 651 - 661. [Abstract] [Full Text] [PDF]

				J. M. Madison Migration of Airway Smooth Muscle Cells Am. J. Respir. Cell Mol. Biol., July 1, 2003; 29(1): 8 - 11. [Full Text] [PDF]

				J. L. Faul, E. A. Demers, C. M. Burke, and L. W. Poulter Alterations in Airway Inflammation and Lung Function During Corticosteroid Therapy for Atopic Asthma* Chest, May 1, 2002; 121(5): 1414 - 1420. [Abstract] [Full Text] [PDF]

				R. Hoontrakoon, H. W. Chu, S. J. Gardai, S. E. Wenzel, P. McDonald, V. A. Fadok, P. M. Henson, and D. L. Bratton Interleukin-15 Inhibits Spontaneous Apoptosis in Human Eosinophils via Autocrine Production of Granulocyte Macrophage-Colony Stimulating Factor and Nuclear Factor-kappa B Activation Am. J. Respir. Cell Mol. Biol., April 1, 2002; 26(4): 404 - 412. [Abstract] [Full Text] [PDF]

				J. BOUSQUET, P. K. JEFFERY, W. W. BUSSE, M. JOHNSON, and A. M. VIGNOLA Asthma . From Bronchoconstriction to Airways Inflammation and Remodeling Am. J. Respir. Crit. Care Med., May 1, 2000; 161(5): 1720 - 1745. [Full Text]

				A. Solomon, R. Shmilowich, D. Shasha, J. Frucht–Pery, J. Pe’er, S. Bonini, and F. Levi–Schaffer Conjunctival Fibroblasts Enhance the Survival and Functional Activity of Peripheral Blood Eosinophils In Vitro Invest. Ophthalmol. Vis. Sci., April 1, 2000; 41(5): 1038 - 1044. [Abstract] [Full Text]

				M. J. Evans, L. S. Van Winkle, M. V. Fanucchi, and C. G. Plopper The Attenuated Fibroblast Sheath of the Respiratory Tract Epithelial-Mesenchymal Trophic Unit Am. J. Respir. Cell Mol. Biol., December 1, 1999; 21(6): 655 - 657. [Full Text]

				M. P. Hallsworth, C. P. C. Soh, C. H. C. Twort, T. H. Lee, and S. J. Hirst Cultured human airway smooth muscle cells stimulated by interleukin-1beta enhance eosinophil survival. Am. J. Respir. Cell Mol. Biol., December 1, 1998; 19(6): 910 - 919. [Abstract] [Full Text]

				F. M. SPOELSTRA, H. HOVENGA, J. A. NOORDHOEK, D. S. POSTMA, and H. F. KAUFFMAN Changes in CD11b and L-selectin Expression on Eosinophils Are Mediated by Human Lung Fibroblasts In Vitro Am. J. Respir. Crit. Care Med., September 1, 1998; 158(3): 769 - 777. [Abstract] [Full Text] [PDF]