Lymphatic vessels in solid organ transplantation and immunobiology

Abstract

endothelial hyaluronan receptor 1; MALT, mucosa-associated lymphoid tissue; mTOR, mechanistic target of rapamycin (also known as mammalian target of rapamycin); mTORC1, mechanistic target of rapamycin complex 1; NFAT, nuclear factor of activated T cells; NFκB, nuclear factor kappa B; NRP2, neuropilin 2; PDPN, podoplanin; PIK3CA, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha; PROX1, prospero homeobox transcription factor 1; SLO, secondary lymphoid organ; TGFβ1, transforming growth factor beta 1; TLO, tertiary lymphoid organ; TNFα, tumor necrosis factor alpha; VEGF, vascular endothelial growth factor; VEGF-A, vascular endothelial growth factor A; VEGF-C, vascular endothelial growth factor C; VEGF-D, vascular endothelial growth factor D; VEGFR3, vascular endothelial growth factor receptor 3 (known as Flt4 in the mouse).

Effect of Hypoxia Preconditioned Secretomes on Lymphangiogenic and Angiogenic Sprouting: An in Vitro Analysis

“…Quantitative analysis of angiogenic/lymphangiogenic growth factor concentration in blood-derived secretomes showed an increased concentration of VEGF-C in hypoxia preconditioned plasma (HPP) and hypoxia preconditioned serum (HPS) compared to their baseline level in fresh plasma and fresh serum, respectively ( Figure 2 A). It is known that, similar to blood vessel formation, the growth of lymphatic vessels is primarily mediated by vascular endothelial growth factor VEGF-C/VEGFR-3 signaling [ 11 , 19 ]. The current data verifies the positive effect of hypoxic conditioning on optimizing the pro-angiogenic/lymphangiogenic composition of blood-derived secretomes, shown here by the significant increase in HPS VEGF level compared to normal serum, and the significantly lower concentration of platelet-derived angiogenic inhibitors TSP-1 and PF-4 in HPP compared to HPS ( Figure 2 ).…”

“…Despite the lack of an adequate body of research work, it is becoming increasingly evident that the complex cell-growth factor interactions, which are known to play catalytic roles in angiogenesis, appear to be involved in lymphangiogenesis as well [ 17 ]. For example, the VEGF family of protein factors, i.e., VEGF-A, -C, and -D can induce the outgrowth of lymphatic vessels [ 18 ], while VEGF-C/VEGFR-3 signaling is a primary mediator of lymphangiogenesis [ 11 , 19 ]. Moreover, the angiogenesis-related growth factors fibroblast growth factor 2 (FGF-2), insulin-like growth factor 1 (IGF-1), IGF-2, hepatocyte growth factor (HGF), endothelin-1 (ET-1), and PDGF-B have all been reported to induce lymphangiogenesis in different contexts [ 5 , 20 ].…”

Lymphatic Reconstruction in Kidney Allograft Aggravates Chronic Rejection by Promoting Alloantigen Presentation

“…In the surgery of organ transplant, the surgeon would not connect the LVs of donor organ to the recipient, which means that the lymphatic network of the transplanted organ is spontaneously rebuilt by the recipient through some kinds of mechanisms ( 33 , 34 ). The LVs from donor kidney have not reconnected to recipient in renal transplant, and this procedure of how they rebuild interrupted lymph drainage after surgery remains to be poorly understood ( 35 ).…”

Lymphatic Vessel Regression and Its Therapeutic Applications: Learning From Principles of Blood Vessel Regression

“…Despite the advent of human leukocyte antigen matching and the administration of immunosuppressants, allograft rejection remains the leading cause of graft failure beyond 1 year post-transplantation ( Yamakawa et al, 2018 ; Wong, 2020 ). Lymphangiogenesis has been observed following transplantation of solid organs such as the heart, kidney, and lungs as well as the normally avascular cornea ( Wong, 2020 ; Hou et al, 2021 ).…”