Parenchymal trafficking of pleural mesothelial cells in idiopathic pulmonary fibrosis

Abstract

Idiopathic pulmonary fibrosis (IPF) is characterized by myofibroblast proliferation leading to architectural destruction. Neither the origin nor the continued proliferation of myofibroblasts is well understood.

Explanted human IPF lungs were stained by immunohistochemistry for calretinin, a marker of pleural mesothelial cells (PMCs). COPD and CF lungs acted as controls. The number of PMCs per 100 nucleated cells and per photomicrograph was estimated along with the Ashcroft score of fibrosis. Mouse PMCs expressing green fluorescent protein (GFP), and those labeled with nanoparticles, were injected into the pleural space of mice given intranasal TGFβ1. Mouse lungs were lavaged and examined for the presence of GFP, α-smooth muscle actin (αSMA), and calretinin.

Calretinin-positive PMCs were found throughout IPF lungs, but not in COPD or CF. The number of PMCs correlated with the Ashcroft score. In mice, nanoparticle-laden PMCs were recoverable by bronchoalveolar lavage, depending on TGFβ1 dose. Fluorescent staining showed αSMA expression in GFP-expressing PMCs, with colocalization of GFP and αSMA.

PMCs can traffic through the lung and show myofibroblast phenotypic markers. PMCs are present in IPF lungs, and their number correlates with IPF severity. Since IPF presumably begins subpleurally, PMCs could play a pathogenetic role via mesothelial-mesenchymal transition.