Different Expression of Endothelin in the Bronchoalveolar Lavage in Patients with Pulmonary Diseases

Abstract

Endothelin (ET) is a broncho- and vasoconstrictive cytokine, but it also possesses proinflammatory and mitogenic activity. It is suggested to be involved in the pathogenesis of fibrotic lung diseases. We analyzed the concentration of ET 1 in the bronchoalveolar lavage (BAL) fluid in 95 patients with different lung diseases, among them 41 patients with interstitial lung diseases (13 fibrosing alveolitis in systemic sclerosis (FASS), 9 idiopathic pulmonary fibrosis (IFP), 8 sarcoidosis (S), 6 occupational lung disease (OLD), 5 other alveolitidies A), 27 patients with pneumonia, and 8 patients with chronic obstructive pulmonary disease (COPD). A heterogeneous group of 19 patients served as controls. The median ET concentration was 3.3 pg/ml. Significantly higher concentration was found in patients with FASS (5.8 pg/ml), IPF (5.0 pg/ml), and S (5.1 pg/ml) compared with OLD (2.8 pg/ml), A (1.9 pg/ml), COPD (1.5 pg/ml), and the control group (2.5 pg/ml). In pneumonia, the elevated ET concentration (4.1 pg/ml) was accompanied by a high alveolocapillary leakage. When normalized to BAL albumin concentration, only FASS presented with significantly elevated ET/albumin in the BAL compared with the control group (134.5 vs. 56.l pg/mg, p < 0.05). There were no correlations between ET and BAL differential cell count or pulmonary function tests. In current smokers, ET in BALF was significantly higher compared with non- or ex-smokers (3.9 vs. 2.0 pg/ml, p < 0.01), but not so the ET/albumin ratio (65.0 vs. 62.5 pg/mg). In summary, ET in the BAL is differentially expressed in distinct inflammatory and interstitial lung disease. Consistently high concentrations are found in FASS and elevated ET concentration could be discussed in IPF, sarcoidosis, and pneumonia. ET concentration in BAL is influenced by current smoking habits.

Endothelin-1 and Transforming Growth Factor-β1 Independently Induce Fibroblast Resistance to Apoptosis via AKT Activation

“…The observed concentrations of active ET-1 are consistent with those reported in scleroderma fibroblasts exposed to TGF-b (7,15). Similar concentrations of ET-1 were found in the epithelial lining fluid of patients with ARDS and bronchoalveolar lavage fluid of patients with interstitial lung disease (44)(45)(46). Although the concentration of ET-1 secreted by mesenchymal cells stimulated with TGF-b1 in vitro approximates these levels reported in vivo, the effective concentration of ET-1 within fibrotic tissue remains unclear, and may be markedly higher within the pericellular microenvironment.…”

Treatment of Sarcoidosis-Associated Pulmonary Hypertension

“…An imbalance in vasoconstrictor and vasodilatory mediators among patients with sarcoidosis and PH has also been shown. Increased levels of the potent vasoconstrictor endothelin-1 have been described in BAL fluid 26 and serum 27 in patients with sarcoidosisrelated PH. Another study 16 reported evidence of increased pulmonary production of thromboxane A 2 during a period of vasodilator-induced increase in pulmonary blood flow.…”

Disorders of lung matrix remodeling

“…A second paradigm is that there are pat- terns of chemokine and/or cytokine expression in patient BAL which appear to correlate with progression of the fibrotic process. The group of profibrotic mediators shown in Table 2 are elevated in the BAL and tissues of several of the disorders listed in Table 1, though the majority of studies have been done with patients thought to have IPF (18)(19)(20)(21)(22)(23)(24). Because individual chemokines, cytokines, and leukotrienes act at multiple points and regulate each others' expression levels, determining the importance of any single mediator among these patients remains a challenge.…”