Upregulation of platelet-derived growth factor-A and -B gene expression in alveolar macrophages of individuals with idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is characterized by accu- mulation of alveolar macrophages spontaneously releasing ex- aggerated amounts of the potent mesenchymal cell growth fac- tor platelet-derived growth factor (PDGF). To evaluate the relative contribution of the two PDGF genes to this process, PDGF-A and -B gene transcription rates and mRNA levels were examined in normal and IPF alveolar macrophages. While normal alveolar macrophages constitutively transcribe both PDGF-A and PDGF-B genes, LPS stimulation increases the transcription of both genes more than threefold. Impor- tantly, IPF alveolar macrophages spontaneously transcribe both genes at a rate similar to that observed for normal macro- phages after in vitro stimulation. Consistent with the tran- scription data, normal macrophages contain mRNA for both PDGF-A and -B, but PDGF-B mRNA is 10-fold more abun- dant. Strikingly, in IPF, both PDGF-A and -B mRNA levels were markedly increased, with persistence of the 10-fold domi- nance of PDGF-B mRNA. Thus, the exaggerated release of PDGF by IPF alveolar macrophages is likely modulated by upregulated PDGF gene transcription rates and concomitantly increased mRNA levels and the persistent 10-fold excess of B > A PDGF mRNA suggests that the PDGF released by alveo- lar macrophages is likely mostly of the potent B-chain homo- dimeric form. (J. Clin. Invest. 1990 . 85 :2023-2027.) PDGFv fibrosis * lung -macrophage * transcription -gene regulation platelet-derived growth factor (PDGF),' a 30-kD dimer of two disulfide-linked polypeptides (5-7). In addition to serving as a potent mitogen that stimulates mesenchymal cells to enter and