Lymphatic Precollectors Contain a Novel, Specialized Subpopulation of Podoplaninlow, CCL27-Expressing Lymphatic Endothelial Cells

Abstract

Expression of the lymphoendothelial marker membrane mucoprotein podoplanin (podo) distinguishes endothelial cells of both blood and lymphatic lineages. We have previously discovered two distinct subpopulations of lymphatic endothelial cells (LECs) in human skin that were defined by their cell surface densities of podoplanin and were designated LEC podo-low and LEC -containing precollector vessels constitute a specialized segment of the initial lymphatic microvasculature, and we hypothesize that these LEC podo-low -containing vessels are involved in the trafficking of CCR10 ؉ T cells during skin inflammation.

Interaction of tumor cells and lymphatic vessels in cancer progression

“…10 The sialoglycoprotein podoplanin, used as a marker to distinguish the lymphatic endothelium in both experimental mouse models and in clinical samples, is expressed at high levels in lymphatic capillaries and at lower levels in precollector vessels. 11 Podoplanin is essential for the correct maturation of the vessels, and podoplanin-deficient mouse embryos show a blood --lymphatic vascular mixing phenotype with blood-filled lymphatic vessels. The functions of podoplanin on lymphatic endothelial cells include binding to CLEC-2 receptors expressed on platelets in the circulating blood.…”

Role of Lymphatic Vessels in Tumor Immunity: Passive Conduits or Active Participants?

“…Interestingly, these segments express different levels of podoplanin that is associated with differential chemokine expression [37]. Lymphatic capillaries express high levels of podoplanin as well as the chemokine (C-C motif) ligand 21 (CCL21), which may bind podoplanin and which attracts activated (CCR7 + ) antigen-presenting cells; the coexpression of podoplanin and CCL21 may have important implications for their specific function.…”

“…On the other hand, precollectors express lower levels of podoplanin and secrete CCL27, which recruits memory CCR10 + T cells. In this way, different immune cell types enter lymphatic capillaries at specialized sites [37].…”

The lymphatic vasculature revisited

“…Two populations of LECs that differ in their content of the membrane mucoprotein podoplanin were identified in the dermal microvasculature (11,12): endothelial cells expressing high levels of podoplanin are localized to the initial capillaries, while those with lower levels of podoplanin are found in precollector segments. Interestingly, these two populations are different lineages that differ in gene expression.…”