Abstract Number: PB1652
Meeting: ISTH 2020 Congress
Theme: Platelets and Megakaryocytes » Platelet Function and Interactions
Background: Hepatic sinusoid obstruction syndrome (SOS) is characterized by a drug and/or radiation-induced liver injury. SOS may negatively influence the patients’ outcome after chemotherapy or hematopoietic stem cell transplantation, and is diagnosed by the clinical symptom of hepatomegaly, fluid accumulation, weight gain, and bilirubinemia. We identified C-type lectin-like receptor 2 (CLEC-2) on the surface of platelets as a receptor for platelet-activating snake venom, rhodocytin. Although liver sinusoidal endothelial cell is also reported to express CLEC-2, it is unknown whether CLEC-2 has some roles in the promotion of SOS.
Aims: The aim of this study is to uncover a previously unknown role of CLEC-2 in the pathogenesis of SOS.
Methods: We used monocrotaline (MCT)-induced mouse model of SOS. Control rat IgG or 2A2B10 (CLEC-2 depleting antibody) were intravenously injected for two consecutive weeks (n = 10, each group). After confirming the absence of CLEC-2 on the surface of platelets, MCT was intraperitoneally injected. Forty-eight hours after MCT administration, mice were sacrificed, and complete blood count, biochemical examination and liver-tissue section were analyzed.
Results: We checked macroscopic findings and analyzed hepatic injury markers in control and CLEC-2 depleted mice after MCT injection. Interestingly, 5 mice out of 10 in CLEC-2 depleted group showed normal macroscopic appearance, although all mice in the control group showed reddish appearance to some extent, indicating that liver injury was attenuated in CLEC-2 deplete mice. Moreover, the elevation of total bilirubin, the most important criterion for the diagnosis of SOS, was significantly decreased in CLEC-2-depleted mice (Figure). The elevation of ALT also tended to be attenuated in CLEC-2-depleted mice. In the liver-tissue section, injury score, evaluated by the morphological changes, was significantly lowered in CLEC-2-deplete mice.
Conclusions: Absence of CLEC-2 may attenuates SOS by protecting the progression of thrombosis in the liver sinusoids.
[Biochemical examination of the serum obtained from control and CLEC-2-depleted mice.]
To cite this abstract in AMA style:
Otake S, Shirai T, Tsukiji N, Sasaki T, Takano K, Ozaki Y, Suzuki-Inoue K. Emerging Roles of CLEC-2 during Development of Monocrotaline-Induced Liver Injury in Mice [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/emerging-roles-of-clec-2-during-development-of-monocrotaline-induced-liver-injury-in-mice/. Accessed March 21, 2024.« Back to ISTH 2020 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/emerging-roles-of-clec-2-during-development-of-monocrotaline-induced-liver-injury-in-mice/