Eosinophils from patients with blood eosinophilia express transforming growth factor beta 1

Abstract

The infiltration of eosinophils into tissues during pathologic responses is often associated with extracellular matrix alterations such as fibrosis. Transforming growth factor-beta 1 (TGF-beta 1) is a well-characterized multifunctional cytokine known to exert potent effects on the extracellular matrix. In this report, we showed the production of TGF-beta 1 by human eosinophils from patients with blood eosinophilia. Northern blot analysis using RNA isolated from eosinophils purified from a patient with the idiopathic hypereosinophilic syndrome (HES) detected the 2.5-kb TGF-beta 1 transcript. In situ hybridization and immunohistochemistry of leukocytes from two patients with HES and two patients with blood eosinophilia localized TGF-beta 1 messenger RNA (mRNA) and protein to eosinophils. No other cell type contained TGF-beta 1 mRNA by in situ hybridization, whereas other leukocytes contained detectable TGF-beta 1 protein by immunohistochemistry. Eosinophils from four normal donors contained little or no detectable TGF-beta 1 protein by immunohistochemistry, whereas eosinophils from two of these four normal donors labeled weakly for TGF-beta 1 mRNA by in situ hybridization. These results show that eosinophils in the peripheral blood of patients with blood eosinophilia can express TGF-beta 1, but that eosinophils in the blood of normal donors contained little or no TGF-beta 1.

Elevated levels of eosinophil major basic protein in the sera of patients with systemic sclerosis

“…Culture media from eosinophils activated in vitro caused stimulation of normal fibroblast proliferation, suggesting the presence of mitogenic factors secreted by activated eosinophils (29,30). Eosinophils infiltrating the fibrotic lesion in nodular sclerotic Hodgkin's disease, and circulating blood eosinophils from patients with idiopathic hypereosinophilic syndrome, express elevated levels of TGFPl mRNA (31,32). In light of the remarkably potent fibrogenic effects of TGFp in vitro and in vivo, secretion of this cytokine by eosinophils into the circulation or at sites of tissue injury could play an important role in the development of fibrosis.…”

Airway Remodeling in Asthma

“…TGF-β is strongly implicated in airway remodeling and is released by eosinophils at the site of allergic inflammation (129,130). TGF-β promotes metalloproteinase-9 (MMP-9) production, also known as gelatinase B; a metalloproteinase found in BAL fluid as well as plasma from asthmatics (131).…”

TGF-β1 increases permeability of ciliated airway epithelia via redistribution of claudin 3 from tight junction into cell nuclei

“…Enrichment of eosinophils is commonly observed in lungs of patients with atopic asthma [ 3 ] and contributes substantially to airway remodelling [ 46 ]. Eosinophils have been identified as a major source of TGF-β1 in the lung [ 73 ]. Eosinophil-derived TGF-β1 was identified as a major factor that triggers tissue remodelling in atopic asthma [ 39 ].…”