Circulating levels of soluble Fas ligand and soluble Fas in patients with chronic obstructive pulmonary disease

Abstract

Fas- and tumour necrosis factor (TNF) receptor-mediated apoptosis are known to be two principal apoptotic mechanisms in humans. Although there are several distinctions between these two systems, in vitro studies have demonstrated similar hypoxic activation and a functional relationship. Since patients with chronic obstructive pulmonary disease (COPD) show chronic hypoxaemia and the activation of the TNF-alpha system, we investigated whether these pathophysiological changes influence the Fas-Fas ligand system. We measured the circulating soluble Fas ligand (sFas-L) level, an inducer of apoptosis, and the soluble Fas receptor (sFas) level, an inhibitor of apoptosis, in 34 COPD patients and 35 age-matched healthy controls. In addition, we investigated the relationships between the levels of sFas-L or sFas and clinical variables including the TNF-alpha system; circulating TNF-alpha and soluble TNF-receptor (sTNF-Rs: sTNF-R55 and R75) levels, in the COPD patients. Although circulating TNF-alpha, sTNF-R55 and R75 levels were significantly higher in the COPD patients than in the healthy controls, serum level of sFas-L (Fisher's exact probability test; P = 0.26) and plasma level of sFas [COPD patients vs. controls; mean (SD); 3.74 (0.63) vs. 3.67 (0.48) ng/ml; P = 0.89) were not increased in the COPD patients. There was no significant correlation between the levels of sFas-L or sFas and clinical variables in COPD patients. These results suggest that the Fas-Fas ligand system does not independently play an important role in the pathophysiology of patients with COPD.

Downregulation of caspases and Fas ligand expression, and increased lifespan of neutrophils after transmigration across intestinal epithelium

“…Consistent with these findings, previous data have shown the presence of a high level of soluble FasL (sFasL) in serum from patients with inflammatory diseases. 40 Moreover, the present work provides evidence suggesting that a decrease in FasL on PMN was involved in the antiapoptotic effect of transmigration, probably by preventing both paracrine and autocrine interactions between Fas and FasL on PMN surface. In this regard, the metalloproteinase inhibitor BB-94 prevented FasL shedding and abrogated the antiapoptotic effect of PMN transepithelial migration.…”

CD40 amplifies Fas-mediated apoptosis: a mechanism contributing to emphysema

“…However, in the context of emphysema, endothelial and epithelial cell apoptosis in COPD were thought to be driven by the release of perforin and granzyme from CD8 ϩ T cells (3,8). The interaction of Fas/FasL system in the development of COPD has long been discussed, only in the context of circulating FasL levels in the patient's serum (34,41), and it remains controversial. However, because CD8…”

Angiotensin II in apoptotic lung injury: potential role in meconium aspiration syndrome

“…29,30 Another group of endogenous mediators believed to play role in apoptosis of parenchymal cells of the lung in COPD is TNF-a, FasL and Fas. However, it is unclear at present whether these molecules are elevated or contribute to the severity of COPD [31][32][33] and more work is needed to clarify these issues.…”