Expression of P-selectin on Endothelial Cells is Upregulated by LPS and TNF-α in Vivo

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Abstract
P-selectin is an endothelial cell adhesion molecule which mediates the binding of neutrophils and monocytes. Its appearance at the cell surface can be induced within minutes by histamine and thrombin which rapidly stimulate the transport of P-selectin from intracellular storage granules to the plasma membrane. We have recently found a second regulation mechanism for P-selectin on mouse endothelioma cells. Like E-seiectin, P-selectin is also regulated at the level of transcription. Both selectins are induced by LPS or TNF-α with a maximal expression level at the cell surface 3–4 h after stimulation. Here, we report that this up-regulation of the synthesis of P-selectin also occurs in vivo in endothelium of the mouse. Analysing brain tissue, which is devoid of constitutive expression of P-selectin, we found that LPS and also TNF-α strongly induce the expression of P-selectin on all venular endothelial cells of the leptomeninges and, at a weaker level, on some blood vessels of the brain parenchyma. Induction of P-selectin expression could also be observed in tissues, such as the tongue, where P-selectin is constitutively expressed on small venules but only rarely on larger venules. Strong staining for P-selectin on endotheiium of all large venules was observed in tissues of LPS and TNF-α treated animals and staining for this newly synthesized P-selectin was enriched at the luminal surface of these cells. Comparison of the expression pattern of LPS-induced P-selectin and E-selectin on blood vessels of the leptomeninges revealed that both selectins were co-induced on venular endothelium while on most arterial endothelial cells only E-selectin and not P-selectin was induced. Thus, in vivo, endothelial cells can differ in their capacity to upregulate the expression of the two endothelial selectins.