Lung lymphatic thrombosis and dysfunction caused by cigarette smoke exposure precedes emphysema in mice. Academic Article uri icon

Overview

abstract

  • The lymphatic vasculature is critical for lung function, but defects in lymphatic function in the pathogenesis of lung disease is understudied. In mice, lymphatic dysfunction alone is sufficient to cause lung injury that resembles human emphysema. Whether lymphatic function is disrupted in cigarette smoke (CS)-induced emphysema is unknown. In this study, we investigated the effect of CS on lung lymphatic function. Analysis of human lung tissue revealed significant lung lymphatic thrombosis in patients with emphysema compared to control smokers that increased with disease severity. In a mouse model, CS exposure led to lung lymphatic thrombosis, decreased lymphatic drainage, and impaired leukocyte trafficking that all preceded the development of emphysema. Proteomic analysis demonstrated an increased abundance of coagulation factors in the lymph draining from the lungs of CS-exposed mice compared to control mice. In addition, in vitro assays demonstrated a direct effect of CS on lymphatic endothelial cell integrity. These data show that CS exposure results in lung lymphatic dysfunction and a shift in thoracic lymph towards a prothrombic state. Furthermore, our data suggest that lymphatic dysfunction is due to effects of CS on the lymphatic vasculature that precede emphysema. These studies demonstrate a novel component of CS-induced lung injury that occurs early in the pathogenesis of emphysema.

publication date

  • March 23, 2022

Research

keywords

  • Emphysema
  • Lung Injury
  • Pulmonary Emphysema
  • Smoke
  • Thrombosis
  • Tobacco Smoke Pollution

Identity

PubMed Central ID

  • PMC8943143

Scopus Document Identifier

  • 85127030740

Digital Object Identifier (DOI)

  • 10.1093/nar/gkab1038

PubMed ID

  • 35322079

Additional Document Info

volume

  • 12

issue

  • 1