Abstract
Pulmonary fibrosis is characterized by accumulation of alveolar macrophages spontaneously releasing exaggerated amounts of the potent mesenchymal cell growth factor platelet-derived growth factor (PDGF) . To evaluate the contribution of the two PDGF genes to this process, PDGF-A and -B gene transcription rates, mRNA levels and protein levels were examined in alveolar macrophages of normals and individuals with idiopathic interstitial pneumonia (TIP) . While nomal alveolar macrophages constitutively transcribed both PDGF-A and -B genes, LPS stimulation significantly increased the transcription of both genes. Interestingly, TIP alveolar macrophages spontaneously transcribed both genes at a rate similar to that observed for LPS-stimulated normal macrophages. Consistent with the transcription data, normal macrophages contained mRNA for both PDGF-A and-B, but PDGF-B mRNA was 10-fold more abundant. Importantly, in TIP, both PDGF-A and-B mRNA levels were markedly increased, with persistence of the 10-fold dominance of PDGF-B mRNA. Furthermore, the immunohistochemical study demonstrated that TIP macrophages contained increased amounts of PDGF molecules with the 10-fold excess of PDGF-B chain> PDGF-A chain.
Thus, the exaggerated release of PDGF by TIP alveolar macrophages is likely modulated by upregulated PDGF gene transcription rates and concomitantly increased mRNA levels, and most of the PDGF molecules released by the alveolar macrophages are likely PDGF-BB homodimers.
