Seiffert Kristina, Ding W, Wagner John A, Granstein Richard D
Department of Dermatology, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10021 USA.
J Invest Dermatol. 2006 May;126(5):1017-27. doi: 10.1038/sj.jid.5700135.
Adenosine 5'-triphosphate (ATP) affects multiple intra- and extracellular processes, including vascular tone and immune responses. Microvascular endothelial cells (EC) play a central role in inflammation by recruitment of inflammatory cells from blood to tissues. We hypothesized that ATP (secreted by neurons and/or released after perturbation of cutaneous cells) may influence secretion of inflammatory messengers by dermal microvascular EC through actions on purinergic P2 receptors. Addition of the hydrolysis-resistant ATP analogue, adenosine 5'-O-(3-thiotriphosphate) (ATPgammaS), to subconfluent cultures of the human microvascular endothelial cell-1 (HMEC-1) cell line led to a dose- and time-dependent increase in release of IL-6, IL-8, monocyte chemoattractant protein-1, and growth-regulated oncogene alpha. Both ATPgammaS-induced release and basal production of these proteins were significantly inhibited by the purinergic antagonists pyridoxal-5'-phosphate-6-azophenyl-2',5'-disulfonic acid (PPADS), pyridoxal-5'-phosphate-6(2'-naphthylazo-6-nitro-4',8'-disulfonate), and suramin. ATPgammaS increased expression of intercellular adhesion molecule-1 (ICAM-1), whereas suramin and PPADS decreased both ATPgammaS-induced and basal ICAM-1 expression. Using PCR, we found that HMEC-1 strongly express mRNA for the P2X(4), P2X(5), P2X(7), P2Y(2), and P2Y(11) receptors and weakly express mRNA for P2X(1) and P2X(3) receptors. Purinergic nucleotides may mediate acute inflammation in the skin and thus contribute to physiological and pathophysiological inflammation. For example, ATP may contribute to both the vasodilation and the inflammation associated with rosacea.
三磷酸腺苷（ATP）影响多种细胞内和细胞外过程，包括血管张力和免疫反应。微血管内皮细胞（EC）通过将炎症细胞从血液募集到组织中，在炎症中起核心作用。我们推测，ATP（由神经元分泌和/或在皮肤细胞受扰动后释放）可能通过作用于嘌呤能P2受体，影响真皮微血管EC分泌炎症信使。将抗水解的ATP类似物5'-O-(3-硫代三磷酸)腺苷（ATPγS）添加到人微血管内皮细胞-1（HMEC-1）细胞系的亚汇合培养物中，导致白细胞介素-6、白细胞介素-8、单核细胞趋化蛋白-1和生长调节致癌基因α的释放呈剂量和时间依赖性增加。嘌呤能拮抗剂5'-磷酸吡哆醛-6-偶氮苯基-2',5'-二磺酸（PPADS）、5'-磷酸吡哆醛-6(2'-萘基偶氮-6-硝基-4',8'-二磺酸盐)和苏拉明显著抑制ATPγS诱导的这些蛋白质的释放以及基础产生。ATPγS增加细胞间黏附分子-1（ICAM-1）的表达，而苏拉明和PPADS降低ATPγS诱导的和基础的ICAM-1表达。通过聚合酶链反应（PCR），我们发现HMEC-1强烈表达P2X(4)、P2X(5)、P2X(7)、P2Y(2)和P2Y(11)受体的信使核糖核酸（mRNA），并弱表达P2X(1)和P2X(3)受体的mRNA。嘌呤能核苷酸可能介导皮肤中的急性炎症，从而导致生理和病理生理炎症。例如，ATP可能导致与酒渣鼻相关的血管舒张和炎症。
