The involvement of Fas-Fas ligand pathway in fibrosing lung diseases

Pulmonary fibrosis begins with alveolitis, which progresses to destruction of lung tissue and excess collagen deposition. This process could be the re sult of DNA damage and a form of apoptosis, Therefore, we hypothesized that Fas ligand (FasL), which induces apoptosis in cells expressing Fas antigen (Fas), is associated with pulmonary fibrosis. We examined frozen lung tiss ues from seven patients with idiopathic pulmonary fibrosis (IPF), and bronc hoalveolar lavage fluid (BALF) cells from 19 patients with IPF and from 17 patients with interstitial pneumonia associated with collagen vascular dise ases (CVD-IP). We used five frozen lungs with normal lung parenchyma and BA LF cells from 10 patients with solitary pulmonary nodule as controls. Rever se transcription-polymerase chain reaction (RT-PCR) showed that Fast messen ger RNA (mRNA) was expressed in BALF cells from all patients with IPF and f rom 15 of 16 patients with CVD-IP. Fast mRNA was not detected in BALF cells except in one of 10 controls. RT in situ PCR detected Fast mRNA in inflamm atory cells in BALF from patients with IPF. Immunohistochemistry detected F ast protein in infiltrating lymphocytes and granulocytes in all of seven fr ozen lung tissues of IPF, but in none of five control lung tissues. Additio nally, the expression of Fas appeared to be upregulated in bronchiolar and alveolar epithelial cells in IPF compared with normal lung parenchyma by im munohistochemistry, We conclude that Fas and Fast were upregulated in fibro sing lung diseases and may associate with DNA damage or apoptosis of bronch iolar and alveolar epithelial cells in this disorder.