A non-human primate derived anti-P-selectin glycoprotein ligand-1 antibody curtails acute pancreatitis by alleviating the inflammatory responses
Acute pancreatitis (AP) is a devastating disease characterized by an inflammatory disorder of the pancreas. P-selectin glycoprotein ligand-1 (PSGL-1) plays a crucial role in the initial steps of the adhesive at process to inflammatory sites, blockade of PSGL-1 might confer potent anti-inflammatory e...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-11-01
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| Series: | Acta Pharmaceutica Sinica B |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211383523002903 |
| _version_ | 1797647930403848192 |
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| author | Yuhan Li Xiangqing Ding Xianxian Wu Longfei Ding Yuhui Yang Xiaoliang Jiang Xing Liu Xu Zhang Jianrong Su Jianqing Xu Zhiwei Yang |
| author_facet | Yuhan Li Xiangqing Ding Xianxian Wu Longfei Ding Yuhui Yang Xiaoliang Jiang Xing Liu Xu Zhang Jianrong Su Jianqing Xu Zhiwei Yang |
| author_sort | Yuhan Li |
| collection | DOAJ |
| description | Acute pancreatitis (AP) is a devastating disease characterized by an inflammatory disorder of the pancreas. P-selectin glycoprotein ligand-1 (PSGL-1) plays a crucial role in the initial steps of the adhesive at process to inflammatory sites, blockade of PSGL-1 might confer potent anti-inflammatory effects. In this study, we generated two non-human primate derived monoclonal antibodies capable of efficiently targeting human PSGL-1, RH001-6 and RH001-22, which were screened from immunized rhesus macaques. We found that RH001-6, can effectively block the binding of P-selectin to PSGL-1, and abolish the adhesion of leukocytes to endothelial cells in vitro. In vivo, we verified that RH001-6 relieved inflammatory responses and pancreatic injury in both caerulein and l-arginine induced AP models. We also evaluated the safety profile after RH001-6 treatment in mice, and verified that RH001-6 did not cause any significant pathological damages in vivo. Taken together, we developed a novel non-human primate derived PSGL-1 blocking antibody with high-specificity, named RH001-6, which can interrupt the binding of PSGL-1 and P-selectin and attenuate inflammatory responses during AP. Therefore, RH001-6 is highly potential to be further developed into therapeutics against acute inflammatory diseases, such as AP. |
| first_indexed | 2024-03-11T15:24:46Z |
| format | Article |
| id | doaj.art-fd8b87e6c0f5485d83787337d19a5afc |
| institution | Directory Open Access Journal |
| issn | 2211-3835 |
| language | English |
| last_indexed | 2024-03-11T15:24:46Z |
| publishDate | 2023-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Acta Pharmaceutica Sinica B |
| spelling | doaj.art-fd8b87e6c0f5485d83787337d19a5afc2023-10-28T05:07:02ZengElsevierActa Pharmaceutica Sinica B2211-38352023-11-01131144614476A non-human primate derived anti-P-selectin glycoprotein ligand-1 antibody curtails acute pancreatitis by alleviating the inflammatory responsesYuhan Li0Xiangqing Ding1Xianxian Wu2Longfei Ding3Yuhui Yang4Xiaoliang Jiang5Xing Liu6Xu Zhang7Jianrong Su8Jianqing Xu9Zhiwei Yang10Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS) & Comparative Medicine Centre, Peking Union Medical College (PUMC), Beijing 100021, China; Department of Clinical Laboratory, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, ChinaShanghai Sinobay Biotechnology Company (Limited), Shanghai 201500, ChinaInstitute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS) & Comparative Medicine Centre, Peking Union Medical College (PUMC), Beijing 100021, ChinaShanghai Public Health Clinical Center, Fudan University, Shanghai 200083, ChinaCapital Medical University, Beijing 100069, ChinaInstitute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS) & Comparative Medicine Centre, Peking Union Medical College (PUMC), Beijing 100021, ChinaInstitute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS) & Comparative Medicine Centre, Peking Union Medical College (PUMC), Beijing 100021, ChinaDepartment of Hepatobiliary Pancreatic Surgery, Zhengzhou University People's Hospital, Henan Provincial People's Hospital, Zhengzhou 450003, ChinaDepartment of Clinical Laboratory, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, ChinaShanghai Sinobay Biotechnology Company (Limited), Shanghai 201500, China; Chongqing Institutes for Life Science Innovation, Chongqing 400715, China; Corresponding authors.Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS) & Comparative Medicine Centre, Peking Union Medical College (PUMC), Beijing 100021, China; Corresponding authors.Acute pancreatitis (AP) is a devastating disease characterized by an inflammatory disorder of the pancreas. P-selectin glycoprotein ligand-1 (PSGL-1) plays a crucial role in the initial steps of the adhesive at process to inflammatory sites, blockade of PSGL-1 might confer potent anti-inflammatory effects. In this study, we generated two non-human primate derived monoclonal antibodies capable of efficiently targeting human PSGL-1, RH001-6 and RH001-22, which were screened from immunized rhesus macaques. We found that RH001-6, can effectively block the binding of P-selectin to PSGL-1, and abolish the adhesion of leukocytes to endothelial cells in vitro. In vivo, we verified that RH001-6 relieved inflammatory responses and pancreatic injury in both caerulein and l-arginine induced AP models. We also evaluated the safety profile after RH001-6 treatment in mice, and verified that RH001-6 did not cause any significant pathological damages in vivo. Taken together, we developed a novel non-human primate derived PSGL-1 blocking antibody with high-specificity, named RH001-6, which can interrupt the binding of PSGL-1 and P-selectin and attenuate inflammatory responses during AP. Therefore, RH001-6 is highly potential to be further developed into therapeutics against acute inflammatory diseases, such as AP.http://www.sciencedirect.com/science/article/pii/S2211383523002903Acute pancreatitisPSGL-1Non-human primateMonoclonal antibodyTherapeutic antibody RH001-6Adhesion of leukocytes to endothelial cells |
| spellingShingle | Yuhan Li Xiangqing Ding Xianxian Wu Longfei Ding Yuhui Yang Xiaoliang Jiang Xing Liu Xu Zhang Jianrong Su Jianqing Xu Zhiwei Yang A non-human primate derived anti-P-selectin glycoprotein ligand-1 antibody curtails acute pancreatitis by alleviating the inflammatory responses Acta Pharmaceutica Sinica B Acute pancreatitis PSGL-1 Non-human primate Monoclonal antibody Therapeutic antibody RH001-6 Adhesion of leukocytes to endothelial cells |
| title | A non-human primate derived anti-P-selectin glycoprotein ligand-1 antibody curtails acute pancreatitis by alleviating the inflammatory responses |
| title_full | A non-human primate derived anti-P-selectin glycoprotein ligand-1 antibody curtails acute pancreatitis by alleviating the inflammatory responses |
| title_fullStr | A non-human primate derived anti-P-selectin glycoprotein ligand-1 antibody curtails acute pancreatitis by alleviating the inflammatory responses |
| title_full_unstemmed | A non-human primate derived anti-P-selectin glycoprotein ligand-1 antibody curtails acute pancreatitis by alleviating the inflammatory responses |
| title_short | A non-human primate derived anti-P-selectin glycoprotein ligand-1 antibody curtails acute pancreatitis by alleviating the inflammatory responses |
| title_sort | non human primate derived anti p selectin glycoprotein ligand 1 antibody curtails acute pancreatitis by alleviating the inflammatory responses |
| topic | Acute pancreatitis PSGL-1 Non-human primate Monoclonal antibody Therapeutic antibody RH001-6 Adhesion of leukocytes to endothelial cells |
| url | http://www.sciencedirect.com/science/article/pii/S2211383523002903 |
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