Soluble form of fas and fas ligand in BAL fluid from patients with pulmonary fibrosis and bronchiolitis obliterans organizing pneumonia.
OBJECTIVE
The Fas-Fas ligand (FasL) pathway is a representative system of apoptosis-signaling receptor molecules. We previously described that this pathway may play an important role in the pathogenesis of fibrosing lung diseases. In this study, we hypothesized that soluble form of Fas (sFas) and FasL (sFasL) may also be associated with this disorder.


RESULTS
We measured sFas and sFasL levels in BAL fluid (BALF) from patients with idiopathic pulmonary fibrosis (IPF), interstitial pneumonia associated with collagen vascular diseases (CVD-IP), and bronchiolitis obliterans organizing pneumonia (BOOP), using enzyme-linked immunosorbent assay. BALF from all patients was obtained before prednisolone therapy. sFasL levels were relatively increased in IPF patients (p = 0.084), and significantly increased in CVD-IP patients (p < 0.05) and BOOP patients (p < 0.05), compared with control subjects. BALF sFasL levels were elevated in the IPF or CVD-IP subgroups with an indication for prednisolone therapy, compared with those without an indication for therapy. The BALF sFasL level in IPF patients was correlated with the number of total cells and lymphocytes. The BALF sFasL level in BOOP patients was relatively or significantly correlated with the number of total cells or lymphocytes, respectively. The BALF sFas level was significantly increased in BOOP patients, but not in IPF or CVD-IP patients.


CONCLUSIONS
We conclude that BALF sFasL levels may be associated with the accumulation of inflammatory cells and reflect the degree of lymphocyte alveolitis in IPF. The elevation of sFasL may be associated with the deterioration of IPF and CVD-IP. The elevation of the BALF sFas level may abrogate the cytotoxicity of FasL in BOOP patients, which may be associated with better prognosis of BOOP, compared with IPF or CVD-IP.
Kuwano
K
K
Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. kkuwano@kokyu.med.kyushu-u.ac.jp
Kawasaki
M
M
Maeyama
T
T
Hagimoto
N
N
Nakamura
N
N
Shirakawa
K
K
Hara
N
N
D000368:Aged; D017209:Apoptosis; D015415:Biomarkers; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry* / Q000166:cytology; D002452:Cell Count; D018549:Cryptogenic Organizing Pneumonia / Q000378:metabolism* / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D004848:Epithelium / Q000378:metabolism / Q000473:pathology; D053222:Fas Ligand Protein; D005260:Female; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008875:Middle Aged; D011379:Prognosis; D011650:Pulmonary Alveoli / Q000378:metabolism / Q000473:pathology; D011658:Pulmonary Fibrosis / Q000378:metabolism* / Q000473:pathology; D019014:fas Receptor / Q000378:metabolism*
D015415:Biomarkers; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D019014:fas Receptor