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- Title
Delay of acute intracellular pH recovery after acidosis decreases endothelial cell activation.
- Authors
Huck, Volker; Niemeyer, André; Goerge, Tobias; Schnaeker, Eva-Maria; Ossig, Rainer; Rogge, Phillip; Schneider, Matthias F.; Oberleithner, Hans; Schneider, Stefan W.
- Abstract
Reperfusion after ischemic conditions induces massive endothelial cell (EC) activation, an initial step of reperfusion injury. Reperfusion is characterized by reoxygenation, realkalinization and a localized increase of inflammatory stimuli. In this study, we focused on the influence of extracellular realkalinization on human umbilical vein endothelial cell (HUVEC) activation. We examined intracellular pH (pHin) and intracellular free calcium concentration ([Ca2+]in), a second messenger known to mediate von Willebrand factor (VWF) exocytosis in endothelium, upon realkalinization. Furthermore, we measured the agonist-stimulated exocytosis of VWF, Interleukin-8 and soluble P-selectin (sP-Selectin) as markers of EC activation. To verify a morphological correlate of EC activation, we finally observed platelet-endothelial adherence during realkalinization using shear flow. Realkalinization of HUVEC was simulated by switching from bicarbonate buffered Ringer solution of an acidotic pHex of 6.4 to a physiologic pHex of 7.4. Extracellular realkalinization was accompanied by pHin recovery from 6.5 to 7.2 within 10 min. Application of cariporide, an inhibitor of the Na+/H+ exchanger subtype 1 (NHE), during extracellular realkalinization significantly delayed the early kinetics of intracellular realkalinization. Histamine stimulated [Ca2+]in was significantly increased upon realkalinization compared to control cells. Also agonist-stimulated release of VWF, Interleukin-8 and sP-Selectin was massively enhanced during pHin recovery in comparison to control. Furthermore, we observed an increased platelet binding to endothelium. Interestingly, each of these realkalinization-induced effects were significantly reduced by early application of cariporide. Therefore, delay of acute NHE-dependent pHin recovery may represent a promising mechanism for inhibition of EC activation upon reperfusion. J. Cell. Physiol. 211: 399–409, 2007. © 2006 Wiley-Liss, Inc.
- Subjects
REPERFUSION; ACIDOSIS; VON Willebrand factor; BLOOD coagulation factors; EXOCYTOSIS
- Publication
Journal of Cellular Physiology, 2007, Vol 211, Issue 2, p399
- ISSN
0021-9541
- Publication type
Article
- DOI
10.1002/jcp.20947