Rationale: Alveolar macrophages are inflammatory cells that may contribute to the pathogenesis of idiopathic pulmonary fibrosis (IPF), which is characterized by excessive alveolar aggregation of cells and extracellular matrix proteins.

Objectives: To identify potential molecular mechanisms of IPF.

Methods: To examine large-scale gene expression, messenger RNA isolated from alveolar macrophages and peripheral blood mononuclear cells from subjects with IPF and normal volunteers was hybridized to cDNA filters.

Measurements and Main Results: We showed that in IPF there is global down-regulation of gene expression in alveolar macrophages but not in blood monocytes. Nuclear run-on and pulse-chase studies showed that alveolar macrophages had significantly reduced transcription (p < 0.01). No significant difference in RNA degradation was found between subjects with IPF and normal volunteers. Western blot analyses revealed that concentrations of transcription factor II-H, a general transcription factor, were significantly lower in alveolar macrophages from subjects with IPF than in those from normal volunteers (p = 0.012).

Conclusions: Impaired transcription in IPF is associated with decreased concentrations of transcription factor II-H in alveolar macrophages and may alter the intraalveolar milieu in IPF.