Abstract
BackgroundDe novo lymphatic vessel formation has recently been observed in lungs of patients with moderate chronic obstructive pulmonary disease (COPD). However, the distribution of lymphatic vessel changes among the anatomical compartments of diseased lungs is unknown. Furthermore, information regarding the nature of lymphatic vessel alterations across different stages of COPD is missing. This study performs a detailed morphometric characterization of lymphatic vessels in major peripheral lung compartments of patients with different severities of COPD and investigates the lymphatic expression of molecules involved in immune cell trafficking.MethodsPeripheral lung resection samples obtained from patients with mild (GOLD stage I), moderate-severe (GOLD stage II-III), and very severe (GOLD stage IV) COPD were investigated for podoplanin-immunopositive lymphatic vessels in distinct peripheral lung compartments: bronchioles, pulmonary blood vessels and alveolar walls. Control subjects with normal lung function were divided into never smokers and smokers. Lymphatics were analysed by multiple morphological parameters, as well as for their expression of CCL21 and the chemokine scavenger receptor D6.ResultsThe number of lymphatics increased by 133% in the alveolar parenchyma in patients with advanced COPD compared with never-smoking controls (p < 0.05). In patchy fibrotic lesions the number of alveolar lymphatics increased 20-fold from non-fibrotic parenchyma in the same COPD patients. The absolute number of lymphatics per bronchiole and artery was increased in advanced COPD, but numbers were not different after normalization to tissue area. Increased numbers of CCL21- and D6-positive lymphatics were observed in the alveolar parenchyma in advanced COPD compared with controls (p < 0.01). Lymphatic vessels also displayed increased mean levels of immunoreactivity for CCL21 in the wall of bronchioles (p < 0.01) and bronchiole-associated arteries (p < 0.05), as well as the alveolar parenchyma (p < 0.001) in patients with advanced COPD compared with never-smoking controls. A similar increase in lymphatic D6 immunoreactivity was observed in bronchioles (p < 0.05) and alveolar parenchyma (p < 0.01).ConclusionsThis study shows that severe stages of COPD is associated with increased numbers of alveolar lymphatic vessels and a change in lymphatic vessel phenotype in major peripheral lung compartments. This novel histopathological feature is suggested to have important implications for distal lung immune cell traffic in advanced COPD.
Highlights
De novo lymphatic vessel formation has recently been observed in lungs of patients with moderate chronic obstructive pulmonary disease (COPD)
Podoplanin is a suitable marker for lung lymphatic vessels In initial studies antibodies against Lymphatic vessel endothelial Rabbit polyclonal hyaluronan receptor-1 (LYVE-1) and podoplanin were evaluated for proper identification of lymphatic vessels in routine paraffin-embedded human lung sections
Lymphatic vessels have an altered expression profile of CC chemokine ligand 21 (CCL21) and D6 in advanced COPD Since lymphatic vessels were increased in numbers in peripheral lungs of patients with advanced COPD we investigated if these changes were associated with altered lymphatic endothelial expression of molecules known to regulate leukocyte entry into the lymphatics
Summary
De novo lymphatic vessel formation has recently been observed in lungs of patients with moderate chronic obstructive pulmonary disease (COPD). This study performs a detailed morphometric characterization of lymphatic vessels in major peripheral lung compartments of patients with different severities of COPD and investigates the lymphatic expression of molecules involved in immune cell trafficking. Several studies have revealed increased numbers of lymphocytes [6,7], mast cells [8], dendritic cells [9,10], and ectopic lymphoid aggregates in peripheral lungs of patients with COPD [11,12,13]. The lymphatic vessels are, apart from their role in interstitial fluid homeostasis, critical for transporting antigen-loaded dendritic cells and memory/effector Tcells to draining lymph nodes where they initiate adaptive immune responses [14,15,16]. It is likely that lung lymphatic vessels transport leukocytes to the ectopic lymphoid aggregates in COPD lungs
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
