Lymphangiogenesis in COPD: another link in the pathogenesis of the disease

Respir Med. 2012 May;106(5):687-93. doi: 10.1016/j.rmed.2011.11.011. Epub 2011 Dec 6.

Abstract

Background: New lymphatic vessels are associated with tissue injury and repair. Recent studies have shown increased lymphatic follicles formation in the lungs of COPD patients. We hypothesized that lymphatic vascular remodeling could be part of COPD pathogenesis.

Aim: To investigate the lymphangiogenetic process in COPD we measured the lymphatic microvessel density (LMVD), the lymphatic invasion (L.I), and their correlation with clinical and laboratory parameters.

Methods: Lung tissue from 20 COPD patients and 20 non-COPD smokers was immunohistochemically stained for D2-40 (lymphatic endothelial cell marker), and LYVE-1 (lymphatic endothelial hyaluronan receptor 1). Both groups had similar age and smoking history.

Results: D2-40 and LYVE-1 were expressed in all specimens. Lymphatic invasion was presented only in COPD specimens. Lymphatic microvessel density (LMVD) as revealed by D2-40 and LYVE-1 markers was statistically significantly higher in COPD patients when compared with non-COPD smokers. Both markers (D2-40, LYVE-1) were correlated with FEV1 (% pred) (R(2) = 0.415, R(2) = 0.605, respectively).

Conclusions: We report for the first time high lymphatic microvessel density and lymphatic invasion in COPD patients, related to the degree of airway obstruction. Our findings could provide novel insights in the pathogenesis of the disease.

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal, Murine-Derived / metabolism
  • Biomarkers / metabolism
  • Endothelium, Lymphatic / metabolism
  • Endothelium, Lymphatic / pathology
  • Female
  • Forced Expiratory Volume / physiology
  • Humans
  • Lymphangiogenesis / physiology*
  • Lymphatic Vessels / metabolism
  • Lymphatic Vessels / pathology
  • Male
  • Middle Aged
  • Pulmonary Disease, Chronic Obstructive / metabolism
  • Pulmonary Disease, Chronic Obstructive / pathology
  • Pulmonary Disease, Chronic Obstructive / physiopathology*
  • Retrospective Studies
  • Smoking / pathology
  • Smoking / physiopathology
  • Vesicular Transport Proteins / metabolism

Substances

  • Antibodies, Monoclonal, Murine-Derived
  • Biomarkers
  • LYVE1 protein, human
  • Vesicular Transport Proteins
  • monoclonal antibody D2-40