Study Of Lymphatic Vessels Research Articles

Renal Interstitial Lymphangiogenesis in Renal Fibrosis.

The basic physiological functions of the lymphatic system include absorption of water and macromolecular substances in the interstitial fluid to maintain the fluid homeostasis, promoting the intestinal absorption of nutrients such as lipids and vitamins from food. Recent studies have found that lymphangiogenesis is associated with some pathological conditions, such as tumor metastasis, injury repair, and chronic inflammation. For a long time, the study of lymphatic vessels (LVs) has been stagnant because of the lack of lymphatic-specific cytology and molecular markers. Renal interstitial lymphangiogenesis is found in patients with chronic kidney disease (CKD) and a series of animal models of renal fibrosis. Intervention of the formation or maturation of LVs in renal tissue of CKD may reduce the drainage of inflammatory cells, attenuate chronic inflammation, delay the progression of renal fibrosis, and improve renal function. This review will summarize the latest findings on renal interstitial lymphangiogenesis in CKD.

Corneal Lymphangiogenesis: Implications in Immunity

The lymphatic system is a network of vessels throughout the body that serves to return lymphatic fluid to the systemic blood circulation and serves as the immune system's highway in the afferent limb of the immune response. This paper reviews the basics of structure, function and development of the lymphatic system. The emphasis is on understanding the role of lymphatics in the cornea as related to angiogenesis and the clinical setting of corneal transplant rejection.The lymphatic system has two main functions: to drain excess extracellular fluid from capillary beds to return to the systemic blood circulation and to capture antigen for presentation to the immune system in the lymphoid compartment (e.g. nodes) connected in parallel to the lymphatic system. The normal cornea is devoid of lymphatic vessels and blood vessels, thus allowing for its unique immune privileged status. Abnormal blood vessel growth into the cornea has been studied for many years, but the study of lymphatic vessels has been hampered until the recent discovery of lymphatic-specific markers. Subsequent studies of vascularized corneas support the presence of lymphatic vessels in the cornea. The growth of new lymphatic (lymphangiogenesis) and blood (hemangiogenesis) vessels in the cornea is closely related to the abrogation of the immune privileged status of the cornea. This review summarizes our current understanding of the parallel development of hemangiogenesis and lymphangiogenesis as related to the mechanisms of immune rejection of corneal transplants.

Lymphangiogenesis Does Not Occur in Breast Cancer

Breast cancer metastasis predominantly occurs via lymphatic vessels. However, the study of lymphatic vessels and lymphangiogenesis has been hampered by lack of specific markers. Recently, antibodies directed against M2A (D2-40), Podoplanin, and Prox-1 that specifically mark lymphatic vessels in paraffin-embedded sections have become available. These were used to study lymphangiogenesis in archival paraffin sections of normal breast (n = 23), fibrocystic disease (n = 7), ductal carcinoma in situ (n = 32), invasive ductal carcinoma (n = 50), and invasive lobular carcinoma (n = 5). In addition, endothelial proliferation in lymphatic vessels was analyzed by dual-color immunohistochemistry with D2-40 and proliferating cell nuclear antigen (PCNA). Expression of D2-40, Prox-1, and Podoplanin was seen in lymphatic vessels but not in blood vessels. Lymphatic vessels were seen in the peritumoral area and as "entrapped" intratumoral vessels adjacent to preexisting normal lobules and ducts. Unlike angiogenesis, there was no increase of lymphatic vessel density in association with neoplastic transformation. On the contrary, a marked reduction in intratumoral lymphatic vessel density was seen in comparison to normal breast tissue, fibrocystic disease, and ductal carcinoma in situ (P = 0.0001). There was an increase in peritumoral lymphatic vessel density as compared with normal breast (P = 0.0001). However, the endothelial cells in the "entrapped" or the peritumoral lymphatic vessels did not show any expression of PCNA indicating minimal or no proliferative activity. This was in contrast to the strong expression seen in adjacent tumor cells and blood vessel endothelial cells. Thus, lymphangiogenesis was not evident when studied by lymphatic vessel density or by lymph vessel endothelial proliferation.

Differential Prox-1 and CD 31 expression in mucousae, cutaneous and soft tissue vascular lesions and tumors

The study of lymphatic vessels and lymphatic tumors has been hampered with difficulty due to the overlapping morphological features between blood and lymphatic endothelial cells, as well as to the lack of specific lymphatic endothelial markers. Over the last few years, lymphatic vessels and lymphangiogenesis have received great attention owing to their putative implications in terms of metastatic dissemination and the promise of targets for lymphangiogenic therapy. Prox-1 is a nuclear transcription factor that plays a major role during embryonic lymphangiogenesis and is deemed to be a useful marker for differentiating lymphatic endothelial cells from the other blood vessels endothelial cells. Here, we describe a double-immunostaining strategy for formalin-fixed, paraffin-embedded tissues that aims at evaluating the distribution of Prox-1 and CD 31 – a cytoplasmic pan-endothelial marker – in a series of 28 mucousae, cutaneous and soft tissue vascular lesions and tumors, including hemangiomas, lymphangiomas, lymphangiectasia, and Kaposi's sarcomas. Our results showed that in non-lesional mucousae and skin, Prox-1 decorated exclusively the nuclei of endothelial cells in lymphatic vessels. Prox-1 stained almost all the benign lymphatic vascular lesions/tumors (91%) and was absent or only focally positive in 75% of blood vascular tumors. CD 31 stained endothelial cells of blood vessels of superficial and deep dermal plexuses, lymphatics, and all blood vascular lesions/tumors. Kaposi's sarcomas were all positive for both CD 31 and Prox-1 markers. In conclusion, although Prox-1 expression in vascular lesions/tumors was not entirely restricted to tumors with known lymphatic differentiation, CD 31/Prox-1 double-immunolabeling can be used as an adjunct marker to identify lymphatic vessels in routinely processed formalin-fixed, paraffin-embedded samples.