Idiopathic pulmonary fibrosis (IPF) is a chronic lung disorder characterized by fibroblast proliferation and extracellular matrix accumulation. However, studies on fibroblast growth rate and collagen synthesis have given contradictory results. Here we analyzed fibroblast growth rate by a formazan-based chromogenic assay; fibroblast apoptosis by in situ end labeling (ISEL) and propidium iodide staining; percent of alpha-smooth muscle actin (alpha-SMA) positive cells by fluorescence-activated cell sorter; and alpha1-(I) collagen, transforming growth factor (TGF)-beta1, collagenase-1, gelatinases A and B, and tissue inhibitor of metalloproteinase (TIMP)-1, -2, -3, and -4 expression by reverse transcriptase/polymerase chain reaction in fibroblasts derived from IPF and control lungs. Growth rate was significantly lower in IPF fibroblasts compared with controls (13.3 +/- 38.5% versus 294.6 +/- 57%, P < 0.0001 at 13 d). Conversely, a significantly higher percentage of apoptotic cells was observed in IPF-derived fibroblasts (ISEL: 31.9 +/- 7.0% versus 15.5 +/- 7.6% from controls; P < 0.008). alpha-SMA analysis revealed a significantly higher percentage of myofibroblasts in IPF samples (62.8 +/- 25.2% versus 14.8 +/- 11.7% from controls; P < 0.01). IPF fibroblasts were characterized by an increase in pro-alpha1-(I) collagen, TGF-beta1, gelatinase B, and all TIMPs' gene expression, whereas collagenase-1 and gelatinase A expression showed no differences. These results suggest that fibroblasts from IPF exhibit a profibrotic secretory phenotype, with lower growth rate and increased spontaneous apoptosis.

Derangement in pulmonary surfactant or its components and alveolar collapse are common findings in idiopathic pulmonary fibrosis (IPF). Surfactant proteins play important roles in innate host defense and normal function of the lung. We examined associations between IPF and genetic polymorphic variants of surfactant proteins, SP-A1, SP-A2, SP-B, SP-C, and SP-D. One SP-A1 (6A(4)) allele and single nucleotide polymorphisms (SNPs) that characterize the 6A(4) allele, and one SP-B (B1580_C) were found with higher frequency ( P

Pulmonary surfactant and its components are essential for normal lung function and are involved in local host defense. Surfactant protein (SP)-A and SP-D bind to and modulate phagocytosis of Mycobacterium tuberculosis by macrophages. Frequency comparisons of SP marker alleles in tuberculosis patients and healthy control subjects (tuberculin-skin test positive or general population) were performed. Regression analyses of the tuberculosis and the tuberculin-skin test positive groups revealed, on the basis of odds ratios, tuberculosis susceptibility (DA11_C and GATA_3) and protective (AAGG_2) marker alleles. Similarly, between tuberculosis patients and general population control subjects, susceptibility 1A(3), 6A(4), and B1013_A and protective AAGG_1, and AAGG_7 marker alleles were observed. Moreover, interactions were seen between alleles 6A(2) and 1A(3) (P=.0064) and between 1A(3) and B1013_A (P=. 036). The findings indicate a possible involvement of SP alleles in tuberculosis pathogenesis.