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. 1. Introduction Idiopathic pulmonary fibrosis (IPF) is a chronic diffuse lung disease, characterised by progressive deterioration which ultimately leads to death [1]. Apoptosis is an important physiological process for the development and the maintenance of tissue homeostasis which ensures a balance between cellular proliferation and turnover in nearly all tissues [2]. Apoptosis can be activated by two pathways.(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. Fas and TNF-receptor 1 are the two most known death receptors. Connection of death Ligand, such as Fas Ligand to its death receptor leads to receptor polymerisation and activation of adaptor proteins called “activated death domains” which activate procaspase molecules to caspases.(b)The intrinsic pathway which is associated to an increase of mitochondrial permeability and is activated by cellular “stress.” Cellular stress leads to reduced expression of antiapoptotic mitochondrial proteins (bcl-2, bcl-x) and to increased expression of proapoptotic mitochondrial proteins (bak, bax, bim). The reduction of anti-apoptotic proteins causes an increase in
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