Tohoku J. Exp. Med., 2014 February, 232(2)

Interaction of Kupffer Cells and Platelets Determines the Severity of Ischemia-Reperfusion Injury in Steatosis

KOICHI OGAWA,¹ TADASHI KONDO,¹ TAKAFUMI TAMURA,¹ HIDEKI MATSUMURA,¹ KIYOSHI FUKUNAGA,¹ SOICHIRO MURATA¹ and NOBUHIRO OHKOHCHI¹

¹Department of Surgery, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan

Liver steatosis increases the risk of postoperative complications following major liver resection, since the steatotic liver is susceptible to ischemia-reperfusion (IR) injury. However, it is unclear how IR injury changes in relation to the degree of hepatic steatosis. Previously, we reported that interaction between Kupffer cells (KCs) and platelets induced hepatic IR injury. The aim of our present study was to evaluate the relationship between the degree of liver steatosis and IR injury by focusing on the interaction of KCs and platelets. Mild and moderate steatotic liver models were generated in Wistar rats by feeding a choline-deficient diet for 2 and 4 weeks, respectively. The intensity of steatosis was defined based on the proportion of hepatocytes with fatty infiltration: normal (less than 5%), a mild steatosis (5-30%), and moderate steatosis (30-60%). All groups were subjected to 20 min of warm ischemia followed by 120 min of reperfusion. The number of adhesion of KCs to platelets in sinusoids was observed by intravital microscopy. IR injury was evaluated with serum alanine aminotransferase levels, histological findings, and sinusoidal perfusion. Compared to the normal liver, mild steatosis reduced the adhesion of KCs to platelets, inducing the attenuation of IR injury. In contrast, moderate steatosis increased the adhesion of KCs to platelets, aggravating IR injury relative to the normal liver. IR injury in the steatotic liver was notsimply proportional to the degree of steatosis. Mild steatosis ameliorates IR injury compared to the normal liver, whereas moderate steatosis increases IR injury.

keywords —— intravital microscopy; ischemia-reperfusion; Kupffer cell; platelet; steatosis

© 2014 Tohoku University Medical Press

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Tohoku J. Exp. Med., 2014, 232, 105-113

Correspondence: Nobuhiro Ohkohchi, M.D, Ph.D., Department of Surgery, Doctoral Program in Clinical Science, Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8575, Japan.

e-mail: nokochi3@md.tsukuba.ac.jp