GATA2 regulates blood/lymph separation in a platelet ‐dependent and lymphovenous valve‐independent manner

AbstractLymphatic vessels collect interstitial fluid, immune cells and digested lipids and return these bodily fluids to blood through two pairs of lymphovenous valves (LVVs). Like other cardiovascular valves LVVs prevent the backflow of blood into the lymphatic vessels. In addition to LVVs platelets are necessary to prevent the entry of blood into the lymphatic vessels. Platelet thrombi are observed at LVVs suggesting that LVVs and platelets function in synergy to regulate blood/lymphatic separation. However, whether platelets can regulate blood/lymph separation independently of LVVs is not known. We have determined that the lymphatic vasculature-specific deletion of the lymphedema-associated transcription factor GATA2 results in the absence of LVVs without compromising blood/lymph separation. In contrast, deletion of GATA2 from both lymphatic vasculature and hematopoietic stem cells results in the absence of LVVs, reduced number of platelets and blood-filled lymphatic vasculature. These observations suggest that GATA2 promotes blood/lymph separation through platelets. Furthermore, LVVs are the only known sites of interaction between blood and lymphatic vessels. The fact that blood is able to enter the lymphatic vessels of mice lacking LVVs and platelets indicates that under these circumstances the lymphatic and blood vessels are connected at yet to be identified sites.

Source: Microcirculation - October 5, 2022 Category: Research Authors: Md. Riaj Mahamud, Xin Geng, Lijuan Chen, Zoheb Ahmed, Yenchun Ho, R. Sathish Srinivasan Tags: ORIGINAL ARTICLE Source Type: research