SIGN-R1 and complement factors are involved in the systemic clearance of radiation-induced apoptotic cells in whole-body irradiated mice Jin-Yeon Park a , SoHee Loh a , Eun-hee Cho a , Hyeong-Jwa Choi b , Tae-Young Na c , Judee Grace E. Nemeno d , Jeong Ik Lee d , Taek Joon Yoon e , In-Soo Choi f , Minyoung Lee b , Jae-Seon Lee g , Young-Sun Kang a, h, * a Department of Biomedical Science & Technology, Konkuk University, 1 Hwayang-dong, Gwangjin-gu, Seoul,143-701, Republic of Korea b Division of Radiation Effect, Korea Institute of Radiological and Medical Sciences, 215-4, 75 Nowon gil Nowon-Gu, Seoul,139-706, Republic of Korea c College of Pharmacy, Seoul National University,1 Gwanak-ro, Gwanak-gu, Seoul 151-741, Republic of Korea d Regenerative Medicine Laboratory, Department of Veterinary Medicine, College of Veterinary Medicine, Konkuk University, Seoul,143-701, Republic of Korea e Department of Food and Nutrition, Yuhan College, Bucheon, Gyeonggi-do, 422-749, Republic of Korea f Department of Infectious Diseases, College of Veterinary Medicine, Konkuk University, 1 Hwayang-dong, Gwangjin-gu, Seoul, 143-701, Republic of Korea g Department of Biomedical Sciences, College of Medicine, Inha University, Incheon, 400-712, Republic of Korea h Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Konkuk University,1 Hwayang-dong, Gwangjin-gu, Seoul, 143-701, Republic of Korea article info Article history: Received 3 June 2015 Accepted 8 June 2015 Available online 12 June 2015 Keywords: g-irradiation Apoptosis SIGN-R1 Complement Systemic clearance abstract Although SIGN-R1-mediated complement activation pathway has been shown to enhance the systemic clearance of apoptotic cells, the role of SIGN-R1 in the clearance of radiation-induced apoptotic cells has not been characterized and was investigated in this study. Our data indicated that whole-body g-irra- diation of mice increased caspase-3 þ apoptotic lymphocyte numbers in secondary lymphoid organs. Following g-irradiation, SIGN-R1 and complements (C4 and C3) were simultaneously increased only in the mice spleen tissue among the assessed tissues. In particular, C3 was exclusively activated in the spleen. The delayed clearance of apoptotic cells was markedly prevalent in the spleen and liver of SIGN- R1 KO mice, followed by a significant increase of CD11b þ cells. These results indicate that SIGN-R1 and complement factors play an important role in the systemic clearance of radiation-induced apoptotic innate immune cells to maintain tissue homeostasis after g-irradiation. © 2015 Elsevier Inc. All rights reserved. 1. Introduction Billions of cells undergo apoptosis as a part of physiological homeostasis (50 ~ 70  10 9 /each day) and are rapidly removed by professional phagocytes in higher organisms [1]. Delayed clearance of apoptotic cells have been linked with various inflammatory diseases and autoimmune diseases such as atherosclerosis, sys- temic lupus erythematosus, and rheumatoid arthritis [2e4]. Therefore, the rapid clearance of apoptotic cells by phagocytes is important for maintaining tissue homeostasis and for promoting an anti-inflammatory response in an effort to prevent an immune response against self-antigens [5]. In higher organisms, complements, such as C1q and mannose binding lectin, directly bind to apoptotic cells and mediate the opsonization of C3 on apoptotic cells [6]. In addition, professional phagocytes, such as macrophages and immature DCs, efficiently remove billions of apoptotic cells that are generated as a part of physiological homeostasis [7]. Transmembrane pattern-recognition receptors, including specific intercellular adhesion molecule-3- Abbreviations: SIGN-R1, Specific intercellular adhesion molecule-3-grabbing nonintegrin-related gene 1; C3, complement component C3; C4, complement Component C4; CD11b, Cluster of differentiation 11b; FITC, Fluorescein isothiocy- anate; CFSE, Carboxyfluorescein succinimidyl ester; CVF, Cobra venom factor. * Corresponding author. Department of Biomedical Science & Technology, Insti- tute of Biomedical Science & Technology, Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Konkuk University, 1 Hwayang- dong, Gwangjin-gu, Seoul, 143-701, Republic of Korea. E-mail address: kangys1967@naver.com (Y.-S. Kang). Contents lists available at ScienceDirect Biochemical and Biophysical Research Communications journal homepage: www.elsevier.com/locate/ybbrc http://dx.doi.org/10.1016/j.bbrc.2015.06.059 0006-291X/© 2015 Elsevier Inc. All rights reserved. Biochemical and Biophysical Research Communications 463 (2015) 1064e1070