Table 2.
Summary of Human and Animal Clinical and Experimental Observations Regarding Lymphatic Vessel Formation and Their Role in Disorders Affecting the Lungs
| Clinical and Experimental Findings | |
|---|---|
| Embryonic development | |
| Humans | Increased saccular dilation in pulmonary lymphangiectasia (7) |
| Animals | Increased dilated lymphatics with similar phenotype to human pulmonary lymphangiectasia due to embryonic VEGF-C overexpression (7) |
| Decreased lymphatic vessel density due to deletion of Prox1, VEGF-C, CCBE-1, or VEGFR-3 (4, 5) with increased perinatal morbidity | |
| Asthma | |
| Humans | Decreased lymphatic vessel density (8) |
| Animals | Decreased lymphatic vessel density with blockade of VEGFR-3 (10), TNF-α blockade (11), dexamethasone administration (decreasing TNF-α and IL-1β) (11), Th2 secretion of IL-4 and IL-13 through the JAK1 and STAT6 pathways (13), Th1 secretion of IFN-γ (14) |
| COPD | |
| Humans | Increased lymphatic vessel density (15, 16) |
| Interstitial lung disease | |
| Humans | Increased lymphatic vessel density (19, 20) |
| Animals | Newly formed lymphatic vessels after radiation exposure regress with subsequent development of pulmonary fibrosis (21) |
| Unchanged lymphatic vessel density with bleomycin exposure, but evidence of impaired lymphatic vessel function (22) | |
| Lung transplant | |
| Humans | Increased lymphatic vessel density in the setting of acute rejection (22) |
| Animals | VEGF-C induced lymphangiogenesis-attenuated allograft rejection through improved hyaluronan clearance (24) |
| Tuberculosis | |
| Humans | Increased serum VEGF-C (29) |
| Animals | Increased lymphatic vessel density in localized pulmonary tuberculosis infection (27) |
| LECs harbor Mycobacterium tuberculosis (28) |
Definition of abbreviations: CCBE, collagen- and calcium-binding epidermal growth factor domain; COPD, chronic obstructive pulmonary disease; JAK, Janus kinase; LEC, lymphatic endothelial cell; Prox, Prospero-related homeodomain transcription factor; STAT, signal transducer and activator of transcription; Th, T helper cell; VEGF, vascular endothelial growth factor; VEGFR, VEGF receptor.