Background.

Establishing lung lymphatic drainage is thought to be important for successful lung transplantation. To date, there has been a complete absence of knowledge of how lymphatic connections are reestablished after lung transplant, despite evidence suggesting that this does indeed occur. The present study aimed to elucidate whether and how lymphatic anastomosis occurs after lung transplant.

Methods.

An orthotopic murine model of lung transplant using lymphatic reporter mice and whole mount immunohistochemistry was used to evaluate the lymphatic vasculature and donor-host connections after lung transplantation.

Results.

Immunohistochemistry of transplanted lungs demonstrated robust lymphatic vessels, and functional assays demonstrated lymphatic drainage in the transplanted lung that was comparable with that in native lungs. Lymphatic vessels in the donor lung exhibited active sprouting toward the host at the anastomosis within the first 3 days after lung transplantation, with more numerous and complex lymphatic sprouting developing thereafter. Donor lymphatic vessels were numerous at the site of anastomosis by day 14 after lung transplantation and formed physical connections with host lymphatic vessels, demonstrating a mechanism by which lymphatic drainage is reestablished in the transplanted lung.

Conclusions.

Lymphatic drainage after lung transplantation is established by active sprouting of donor lymphatic vessels towards the host and the formation of donor-host lymphatic connections at the level of the transplant anastomosis.