S114 Lymphatic vessel distribution in fibrotic lung diseases

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Abstract

Relatively little is known on lymphatic vessel remodelling in lung fibrosis, and whether differences in lymphatic distribution underlie the worse survival seen in idiopathic pulmonary fibrosis, compared to the other fibrotic interstitial pneumonias. Lymphatic vessel remodelling and a deficit in lymphatic clearance could lead to prolonged exposure to pathogenic antigens and/or pro-inflammatory/pro-fibrotic mediators in the alveolar-interstitial space. In this study, we compared lymphatic and blood vessel morphology in lung biopsies of six patients with idiopathic pulmonary fibrosis (with usual interstitial pneumonia pattern-UIP), six patients with fibrotic non-specific interstitial pneumonia associated with scleroderma (NSIP) five patients with fibrotic organising pneumonia (FOP) and five controls (normal lung peripheral to resected cancer). Consecutive sections were stained with Movat's pentachrome and with double immunostaining for von Willebrand factor (blood vessels) and for podoplanin (lymphatic specific marker D2-40) (see Abstract S114 figure 1). Area, perimeter and position were recorded for all lymphatic vessels and for blood vessels with a diameter >15 μm, to be sure to exclude capillaries. In the three disease groups, blood vessels were significantly smaller (mean diameter: FOP 18±2, NSIP 13±1, UIP 13±1 μm) compared to controls (23±2 μm). Density of lymphatic vessels was significantly reduced in NSIP and UIP (21±2 mm−2), compared to controls (35±4 mm−2) and their size was significantly greater (mean diameter: NSIP 111±10 μm, UIP 121±5 μm, controls: 74±9 μm). In controls, 85±6% of the parenchymal lymphatics were close (<100 μm) to a blood vessel, and only 5±4% were in proximity of bronchoalveolar spaces, while in all three disease groups they were less frequently perivascular (FOP 47±6%, NSIP 55±3%, UIP 56±2%) and more frequently associated with the bronchoalveolar lumen (FOP 52±11%, NSIP 85±3%, UIP 69±2%). Lymphatic vessels were rarely seen inside Masson bodies and never inside fibroblastic foci (Abstract S114 figure 1). These data are consistent with a substantial remodelling of lymphatic vessels in fibrotic lung disease, with a shift of lymphatics away from blood vessels.

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