Exaggerated Spontaneous Release of Platelet-Derived Growth Factor by Alveolar Macrophages from Patients with Idiopathic Pulmonary Fibrosis

TLDR

Idiopathic pulmonary fibrosis is marked by excess mesenchymal cells in alveolar walls, and alveolar macrophages normally express low levels of c‑sis, the gene for platelet‑derived growth factor, which attracts and stimulates these cells. The study aimed to determine whether alveolar macrophages from IPF patients secrete excess platelet‑derived growth factor, potentially driving mesenchymal cell accumulation and fibrosis. The released growth factor was confirmed active by inducing smooth‑muscle cell chemotaxis and acting as a competence factor for fibroblast growth. Alveolar macrophages from IPF patients released fourfold more platelet‑derived growth factor than controls, supporting the idea that this excess mitogen contributes to mesenchymal cell accumulation and fibrosis.

Abstract

Idiopathic pulmonary fibrosis is a fibrotic lung disease characterized by an increased number of mesenchymal cells in the alveolar walls. Alveolar macrophages constitutively express low levels of c-sis, the protooncogene coding for the B chain of platelet-derived growth factor, a protein with chemotactic and mitogenic activity toward mesenchymal cells. We therefore hypothesized that alveolar macrophages in patients with idiopathic pulmonary fibrosis may release increased amounts of platelet-derived growth factor, which might help to explain the accumulation of mesenchymal cells and the fibrosis of the lower respiratory tract in the disease. Evaluation of alveolar macrophages recovered from the lungs of patients with idiopathic pulmonary fibrosis demonstrated that these cells spontaneously released four times more platelet-derived growth factor than did alveolar macrophages recovered from normal persons (P less than 0.01). That the platelet-derived growth factor molecules were potentially active was shown by their chemotactic activity for smooth-muscle cells and their ability to act as a "competence" factor for fibroblast growth. These observations suggest the possibility that the accumulation of mesenchymal cells within the alveolar walls in patients with idiopathic pulmonary fibrosis may result partly from the exaggerated release of the potent mitogen platelet-derived growth factor by mononuclear phagocytes in the lower respiratory tract.