Blockade of KATP channels reduces endothelial hyperpolarization and leukocyte recruitment upon reperfusion after hypoxia

Figura, M., Chilton, L., Liacini, A., Viskovic, M.Maric, Phan, V., Knight, D., Millar, T.M., Patel, K., Kubes , P., Giles, W.R., and Tibbles, L.A. (2009) Blockade of KATP channels reduces endothelial hyperpolarization and leukocyte recruitment upon reperfusion after hypoxia. American Journal of Transplantation, 9 (4). pp. 687-696.

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Abstract

Ischemia/reperfusion injury in renal transplantation leads to slow or initial nonfunction, and predisposes to acute and chronic rejection. In fact, severe ischemia reperfusion injury can significantly reduce graft survival, even with modern immunosuppressive agents. One of the mechanisms by which ischemia/reperfusion causes injury is activation of endothelial cells resulting in inflammation. Although several therapies can be used to prevent leukocyte recruitment to ischemic vessels (e.g. antiadhesion molecule antibodies), there have been no clinical treatments reported that can prevent initial immediate neutrophil recruitment upon reperfusion. Using intravital microscopy, we describe abrogation of immediate neutrophil recruitment to ischemic microvessels by the KATP antagonist glibenclamide (Glyburide™). Further, we show that glibenclamide can reduce leukocyte recruitment in vitro under physiologic flow conditions. ATP-regulated potassium channels (KATP) are important in the control of cell membrane polarization. Here we describe profound hyperpolarization of endothelial cells during hypoxia, and the reduction of this hyperpolarization using glibenclamide. These findings suggest that control of endothelial membrane potential during ischemia may be an important therapeutic tool in avoiding ischemia/reperfusion injury, and therefore, enhancing transplant long-term function.

Item ID: 9647
Item Type: Article (Research - C1)
ISSN: 1600-6143
Keywords: endothelial cell hyperpolarization; ischemia/reperfusion injury; KATP channels; neutrophil recruitment
Date Deposited: 09 Apr 2010 00:26
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110708 Transplantation Immunology @ 50%
11 MEDICAL AND HEALTH SCIENCES > 1102 Cardiovascular Medicine and Haematology > 110201 Cardiology (incl Cardiovascular Diseases) @ 50%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920108 Immune System and Allergy @ 50%
92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920103 Cardiovascular System and Diseases @ 50%
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