Macrophage production of transforming growth factor beta and fibroblast collagen synthesis in chronic pulmonary inflammation.

TLDR

The study used a bleomycin‑induced rat model to examine the relationship between collagen synthesis and TGF‑beta production, and their cellular distribution. Bleomycin was administered intratracheally to induce pulmonary inflammation and fibrosis, and TGF‑beta levels and collagen synthesis were measured over time while mapping cellular localization. TGF‑beta rose within 2 h, peaked 7 days later at 30‑fold above controls, preceded maximal collagen synthesis, and localized mainly to macrophages and extracellular matrix in repair regions, underscoring its pivotal role in fibrosis. Later in the course of the response.

Abstract

A rat model of bleomycin-induced pulmonary inflammation and fibrosis was used to examine the relationship between collagen synthesis and transforming growth factor beta (TGF-beta) production, and cellular distribution. Total lung TGF-beta was elevated within 2 h of intratracheal bleomycin administration and peaked 7 d later at levels 30-fold higher than controls. This was followed by a gradual decline with lower but persistent levels of production in the late phase of the response between 21 and 28 d later. The peak TGF-beta levels preceded the maximum collagen and noncollagen protein synthesis measured by [3H]proline incorporation into lung fibroblast explants of bleomycin-treated rats. The pattern of immunohistochemical staining localized TGF-beta initially in the cytoplasm of bronchiolar epithelium cells and subepithelial extracellular matrix. The peak of lung TGF-beta levels at 7 d coincided with intense TGF-beta staining of macrophages dispersed in the alveolar interstitium and in organized clusters. Later in the course of the response. TGF-beta was primarily associated with extracellular matrix in regions of increased cellularity and tissue repair, and coincided with the maximum fibroblast collagen synthesis. This temporal and spatial relationship between collagen production and TGF-beta production by macrophages suggests an important if not primary role for TGF-beta in the pathogenesis of the pulmonary fibrosis.