Extracellular matrix in normal and fibrotic human lungs.

TLDR

In normal human lungs, type IV collagen and laminin line basement membranes, type III collagen forms ribbonlike patterns in septa, and type I collagen is irregularly distributed. The study used polyclonal affinity‑purified antibodies against collagens I, III, IV and laminin to compare extracellular matrix distribution in 10 normal and 32 abnormal human lungs via indirect immunofluorescence. In fibrotic lung disease, collagens I and III accumulate in the expanded interstitium, with type III dominating early and type I becoming predominant later, while the basement membrane is disrupted early and interstitial collagens invade alveolar spaces; in non‑fibrotic pulmonary disease the ECM pattern remains essentially normal.

Abstract

Polyclonal affinity-purified antibodies to human collagen types I, III, and IV, and laminin were used to compare the extracellular matrix (ECM) in 10 normal and 32 abnormal lungs by indirect immunofluorescence. In normal lungs, type IV collagen and laminin codistributed in a uniform linear pattern along the epithelial and endothelial basement membranes. Type III collagen was found within the alveolar septa and interstitium in an interrupted ribbonlike pattern and was aggregated at the entrance rings of the alveoli. Type I collagen was distributed irregularly within the alveolar wall and was less prominent than type III collagen. In patients with pulmonary disease not characterized by interstitial fibrosis (n = 15), the distribution of ECM components studied was essentially normal. In pulmonary disease in which interstitial fibrosis was the characteristic feature, such as idiopathic pulmonary fibrosis (IPF) and adult respiratory distress syndrome (ARDS) (n = 17), collagen types I and III accumulated in the expanded interstitium. Type III collagen was initially predominant in the thickened alveolar septa and interstitium, whereas type I collagen appeared to be the principal collagen at later stages in the disease course. The basement membrane was disrupted early in the disease course with invasion of the alveolar spaces by interstitial collagens similar in type to those present in the adjacent interstitium.