A Previously Unknown Dermal Blood Vessel Phenotype in Skin Inflammation

Abstract

Podoplanin and lymphatic vascular endothelial hyaluronan receptor-1 (LYVE-1) are considered as lineage markers for lymphatic vessel (LV) endothelial cells (LECs). We have recently shown that IL-3 induces de novo expression of these genes in cultured blood vessel (BV) endothelial cells (BEC). To ask, if this is trans-differentiation or activation, we analyzed inflamed skin samples and cytokine-stimulated organ-cultured skin and found a subset of blood capillaries within the papillary dermis expressing low amounts of podoplanin and LYVE-1 as well as high amounts of cytokine-inducible adhesion molecules. In contrast, neighboring lymphatic capillaries express high amounts of podoplanin, LYVE-1 and low amounts of cytokine-inducible adhesion molecules. The different response patterns to inflammatory stimuli were reproducible in cell culture, when cytokine-stimulated BEC and LEC were analyzed. These findings signify that expression of "lymphatic proteins" on BEC corresponds to cell activation.