Decreased apoptotic rate of alveolar macrophages of patients with idiopathic pulmonary fibrosis.

Fotios Drakopanagiotakis,Areti Xifteri,Demetrios Mermigkis,Andreas Karameris,Konstantina Tsakanika,Evaggelos Tsiambas,Napoleon Karagiannidis,Demosthenes Bouros,Vlasis Polychronopoulos

doi:10.1155/2012/981730

Fotios Drakopanagiotakis, Areti Xifteri + Show 7 more

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https://doi.org/10.1155/2012/981730

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Abstract

Introduction. Increased apoptosis of epithelial cells and decreased apoptosis of myofibroblasts are involved in the pathogenesis of IPF. The apoptotic profile of alveolar macrophages (AMs) in IPF is unclear. Aim. To investigate whether AMs of patients with IPF exhibit a different apoptotic profile compared to normal subjects. Methods. We analyzed, by immunohistochemistry, the expression of the apoptotic markers fas, fas ligand , bcl-2, and bax in AM obtained from bronchoalveolar lavage fluid (BALF) of 20 newly diagnosed, treatment-naive IPF patients and of 16 controls. Apoptosis of AM was evaluated by Apoptag immunohistochemistry. IPF patients received either interferon-g and corticosteroids or azathioprine and corticosteroids for six months. Results. BALF AMs undergoing apoptosis were significantly less in IPF patients. No difference was found in the expression of fas or fas ligand, bcl-2 and bax between IPF and control group. No difference was found between the respiratory function parameters of the two treatment groups after six months. A positive correlation was found between the number of bcl-2 positive stained macrophages and DLCO after treatment. Conclusions. The decreased apoptotic rate of AM of patients with IPF is not associated with decreased expression of apoptosis mediators involved in the external or internal apoptotic pathway.

Highlights

Increased apoptosis of epithelial cells and decreased apoptosis of myofibroblasts are involved in the pathogenesis of Idiopathic pulmonary fibrosis (IPF)
Neutrophils, eosinophils, and mast cells were significantly increased in the bronchoalveolar lavage fluid (BALF) of patients with IPF compared to the control group
We examined the expression of specific apoptotic markers in BALF macrophages of treatment-naive patients and control group, representing activation of the extrinsic and the intrinsic pathway and total expression of apoptosis, based on expression of Apoptag; a statistically significant difference was found between the IPF group and control group at presentation regarding expression of Apoptag

Summary

Introduction

Aim. To investigate whether AMs of patients with IPF exhibit a different apoptotic profile compared to normal subjects. By immunohistochemistry, the expression of the apoptotic markers fas, fas ligand , bcl-2, and bax in AM obtained from bronchoalveolar lavage fluid (BALF) of 20 newly diagnosed, treatment-naive IPF patients and of 16 controls. BALF AMs undergoing apoptosis were significantly less in IPF patients. No difference was found in the expression of fas or fas ligand, bcl-2 and bax between IPF and control group. The decreased apoptotic rate of AM of patients with IPF is not associated with decreased expression of apoptosis mediators involved in the external or internal apoptotic pathway. (a) The extrinsic or death-receptor pathway which involves the activation of death receptors present in the cell membrane, which are activated by death ligands. The reduction of anti-apoptotic proteins causes an increase in mitochondrial membrane permeability

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Conclusion