Lung lymphatic thrombosis and dysfunction caused by cigarette smoke exposure precedes emphysema in mice

Barbara D. Summers, Kihwan Kim, Cristina C. Clement, Zohaib Khan, Sangeetha Thangaswamy, Jacob McCright, Katharina Maisel, Sofia Zamora, Stephanie Quintero, Alexandra C. Racanelli, David Redmond, Jeanine D’Armiento, Jisheng Yang, Amy Kuang, Laurel Monticelli, Mark L. Kahn, Augustine M.K. Choi, Laura Santambrogio, Hasina Outtz Reed

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


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.

Original languageEnglish (US)
Article number5012
Pages (from-to)5012
JournalScientific Reports
Issue number1
StatePublished - Mar 23 2022


  • Animals
  • Emphysema/pathology
  • Humans
  • Lung/pathology
  • Lung Injury/pathology
  • Mice
  • Mice, Inbred C57BL
  • Proteomics
  • Pulmonary Emphysema/pathology
  • Smoke/adverse effects
  • Smoke Inhalation Injury
  • Thrombosis/pathology
  • Tobacco/adverse effects
  • Tobacco Smoke Pollution/adverse effects

ASJC Scopus subject areas

  • General


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