More Than Just Drain Pipes, Pulmonary Lymphatics Play a Pivotal Role in the Development of Bronchiolitis Obliterans Syndrome
1Childrens Hospital of Phila, Philadelphia, PA, 2Children's Hospital of Philadelphia, Philadelphia, PA, 3Weill Cornell, New York, NY
Meeting: 2022 American Transplant Congress
Abstract number: 90
Keywords: Arteriosclerosis, Fibrosis, Lung transplantation
Topic: Basic Science » Basic Science » 07 - Vascular, Lymphatic, Stromal and Parenchymal Cell Biology
Session Information
Session Name: Histocompatibility and Endothelial/Lymphatic Cell Biology
Session Type: Rapid Fire Oral Abstract
Date: Sunday, June 5, 2022
Session Time: 3:30pm-5:00pm
Presentation Time: 4:10pm-4:20pm
Location: Hynes Room 310
*Purpose: Chronic allograft dysfunction (CLAD) remains a major determinant of the generally poor long-term outcome of lung transplantation compared to that of other solid organ transplants. Much attention has been directed towards analysis of the roles of the immune system in development of bronchiolitis obliterans syndrome (BOS) or restrictive allograft syndrome (RAS), in contrast to the relatively little consideration of the contribution of lung parenchymal cells. With regard to the latter, we now report data concerning an important role of pulmonary lymphatic endothelial cells in determining the development of BOS.
*Methods: Left lung allografts were performed using the murine C57BL/B6->C57BL/10 strain combination in which WT donor lungs or those with various gene knockouts were evaluated (n>10/group), including the deletion (DTR/VEGFR3) or proliferation (VGEFR3cre/PTEN) of pulmonary lymphatics.
*Results: Use of iDTR VEGFR-3CreERT2 donor mice to delete pulmonary lymphatics doubled the incidence of post-lung transplant BOS to almost 100% at 30 days (p<0.01). By contrast, donor lung deletion of PTEN led to tonic VEGF stimulation of lymphangiogenesis, as shown by increased Prox1 mRNA and VEGFR3 staining (both p<0.05), and an absence of BOS in 30-day lung allografts (p<0.01). The latter lung allografts showed well-preserved airspaces and accumulations of leukocytes within dilated lymphatics surrounding bronchovascular bundles.
*Conclusions: These studies show that pulmonary lymphatic endothelial cells contribute to the health of lung allografts and help regulate the development of BOS. Our ongoing molecular, biochemical, and cellular studies are directed towards dissecting the interactions of immune cells and pulmonary lymphatics in efforts to understand these diametrically opposed datasets.
To cite this abstract in AMA style:
Wang L, Han R, Reed HOuttz, Hancock WW. More Than Just Drain Pipes, Pulmonary Lymphatics Play a Pivotal Role in the Development of Bronchiolitis Obliterans Syndrome [abstract]. Am J Transplant. 2022; 22 (suppl 3). https://atcmeetingabstracts.com/abstract/more-than-just-drain-pipes-pulmonary-lymphatics-play-a-pivotal-role-in-the-development-of-bronchiolitis-obliterans-syndrome/. Accessed October 6, 2024.« Back to 2022 American Transplant Congress