Evaluation of the immunological functions of placental alkaline phosphatase in vivo using ALPP transgenic mice
Alkaline phosphatase (ALP) is a ubiquitously expressed dephosphorylating enzyme and its level in blood is widely used as a diagnosis marker of liver damage or bone disorders in human patients. ALP is also considered as an anti-inflammatory protein due to its ability to dephosphorylate and inactivate...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2025-02-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1499388/full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832087183187509248 |
|---|---|
| author | Tse-Ching Chen Kwai-Fong Ng Ning Chen Yi-Ling Pan Chun-An Cheng Hsiao-Chun Wu Yi-Jen Hsueh Nien-Yi Chiang Hsi-Hsien Lin Hsi-Hsien Lin Hsi-Hsien Lin Hsi-Hsien Lin |
| author_facet | Tse-Ching Chen Kwai-Fong Ng Ning Chen Yi-Ling Pan Chun-An Cheng Hsiao-Chun Wu Yi-Jen Hsueh Nien-Yi Chiang Hsi-Hsien Lin Hsi-Hsien Lin Hsi-Hsien Lin Hsi-Hsien Lin |
| author_sort | Tse-Ching Chen |
| collection | DOAJ |
| description | Alkaline phosphatase (ALP) is a ubiquitously expressed dephosphorylating enzyme and its level in blood is widely used as a diagnosis marker of liver damage or bone disorders in human patients. ALP is also considered as an anti-inflammatory protein due to its ability to dephosphorylate and inactivate inflammation-triggering molecules such as lipopolysaccharide (LPS). Placental alkaline phosphatase (ALPP) is one of tissue-specific ALP isozymes expressed mostly during pregnancy, however it was found to be differentially upregulated in certain hepatocellular carcinomas by us recently. In addition, ALPP has been identified as a reliable biomarker of diverse germ cell tumors. Nevertheless, little is known of its immune modulatory role in vivo. In this study, we generated ALPP transgenic mice and tested these mice in the LPS-induced sepsis and male-to-female skin graft rejection models. Our results showed that ALPP transgenic mice are more susceptible to intraperitoneal injection of LPS in comparison to control animals. In addition, female ALPP transgenic mice were better at delaying the rejection of male skin grafts. In an in vitro phagocytosis experiment, addition of exogenous ALPP compromised the phagocytic ability of THP-1 monocytic cells. These results indicate that excess ALPP plays a role in modulating both innate and adaptive immune functions. |
| format | Article |
| id | doaj-art-df279e7febbb49c9843765ab7e7fdb01 |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-df279e7febbb49c9843765ab7e7fdb012025-02-06T07:09:09ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-02-011610.3389/fimmu.2025.14993881499388Evaluation of the immunological functions of placental alkaline phosphatase in vivo using ALPP transgenic miceTse-Ching Chen0Kwai-Fong Ng1Ning Chen2Yi-Ling Pan3Chun-An Cheng4Hsiao-Chun Wu5Yi-Jen Hsueh6Nien-Yi Chiang7Hsi-Hsien Lin8Hsi-Hsien Lin9Hsi-Hsien Lin10Hsi-Hsien Lin11Department of Anatomic Pathology, Chang Gung Memorial Hospital-Linkou, Taoyuan, TaiwanDepartment of Anatomic Pathology, Chang Gung Memorial Hospital-Linkou, Taoyuan, TaiwanDepartment of Anatomic Pathology, Chang Gung Memorial Hospital-Linkou, Taoyuan, TaiwanDepartment of Anatomic Pathology, Chang Gung Memorial Hospital-Linkou, Taoyuan, TaiwanDepartment of Anatomic Pathology, Chang Gung Memorial Hospital-Linkou, Taoyuan, TaiwanDepartment of Anatomic Pathology, Chang Gung Memorial Hospital-Linkou, Taoyuan, TaiwanDepartment of Ophthalmology and Center for Tissue Engineering, Chang Gung Memorial Hospital-Linkou, Taoyuan, TaiwanKennedy Institute of Rheumatology, University of Oxford, Oxford, United KingdomDepartment of Anatomic Pathology, Chang Gung Memorial Hospital-Linkou, Taoyuan, TaiwanDepartment of Microbiology and Immunology, Graduate School of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, TaiwanDivision of Rheumatology, Allergy and Immunology, Chang Gung Memorial Hospital-Keelung, Keelung, TaiwanCenter for Molecular and Clinical Immunology, College of Medicine, Chang Gung University, Taoyuan, TaiwanAlkaline phosphatase (ALP) is a ubiquitously expressed dephosphorylating enzyme and its level in blood is widely used as a diagnosis marker of liver damage or bone disorders in human patients. ALP is also considered as an anti-inflammatory protein due to its ability to dephosphorylate and inactivate inflammation-triggering molecules such as lipopolysaccharide (LPS). Placental alkaline phosphatase (ALPP) is one of tissue-specific ALP isozymes expressed mostly during pregnancy, however it was found to be differentially upregulated in certain hepatocellular carcinomas by us recently. In addition, ALPP has been identified as a reliable biomarker of diverse germ cell tumors. Nevertheless, little is known of its immune modulatory role in vivo. In this study, we generated ALPP transgenic mice and tested these mice in the LPS-induced sepsis and male-to-female skin graft rejection models. Our results showed that ALPP transgenic mice are more susceptible to intraperitoneal injection of LPS in comparison to control animals. In addition, female ALPP transgenic mice were better at delaying the rejection of male skin grafts. In an in vitro phagocytosis experiment, addition of exogenous ALPP compromised the phagocytic ability of THP-1 monocytic cells. These results indicate that excess ALPP plays a role in modulating both innate and adaptive immune functions.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1499388/fullplacental alkaline phosphatasephagocytosissepsisskin graft rejectiontransgenic mouse |
| spellingShingle | Tse-Ching Chen Kwai-Fong Ng Ning Chen Yi-Ling Pan Chun-An Cheng Hsiao-Chun Wu Yi-Jen Hsueh Nien-Yi Chiang Hsi-Hsien Lin Hsi-Hsien Lin Hsi-Hsien Lin Hsi-Hsien Lin Evaluation of the immunological functions of placental alkaline phosphatase in vivo using ALPP transgenic mice Frontiers in Immunology placental alkaline phosphatase phagocytosis sepsis skin graft rejection transgenic mouse |
| title | Evaluation of the immunological functions of placental alkaline phosphatase in vivo using ALPP transgenic mice |
| title_full | Evaluation of the immunological functions of placental alkaline phosphatase in vivo using ALPP transgenic mice |
| title_fullStr | Evaluation of the immunological functions of placental alkaline phosphatase in vivo using ALPP transgenic mice |
| title_full_unstemmed | Evaluation of the immunological functions of placental alkaline phosphatase in vivo using ALPP transgenic mice |
| title_short | Evaluation of the immunological functions of placental alkaline phosphatase in vivo using ALPP transgenic mice |
| title_sort | evaluation of the immunological functions of placental alkaline phosphatase in vivo using alpp transgenic mice |
| topic | placental alkaline phosphatase phagocytosis sepsis skin graft rejection transgenic mouse |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1499388/full |
| work_keys_str_mv | AT tsechingchen evaluationoftheimmunologicalfunctionsofplacentalalkalinephosphataseinvivousingalpptransgenicmice AT kwaifongng evaluationoftheimmunologicalfunctionsofplacentalalkalinephosphataseinvivousingalpptransgenicmice AT ningchen evaluationoftheimmunologicalfunctionsofplacentalalkalinephosphataseinvivousingalpptransgenicmice AT yilingpan evaluationoftheimmunologicalfunctionsofplacentalalkalinephosphataseinvivousingalpptransgenicmice AT chunancheng evaluationoftheimmunologicalfunctionsofplacentalalkalinephosphataseinvivousingalpptransgenicmice AT hsiaochunwu evaluationoftheimmunologicalfunctionsofplacentalalkalinephosphataseinvivousingalpptransgenicmice AT yijenhsueh evaluationoftheimmunologicalfunctionsofplacentalalkalinephosphataseinvivousingalpptransgenicmice AT nienyichiang evaluationoftheimmunologicalfunctionsofplacentalalkalinephosphataseinvivousingalpptransgenicmice AT hsihsienlin evaluationoftheimmunologicalfunctionsofplacentalalkalinephosphataseinvivousingalpptransgenicmice AT hsihsienlin evaluationoftheimmunologicalfunctionsofplacentalalkalinephosphataseinvivousingalpptransgenicmice AT hsihsienlin evaluationoftheimmunologicalfunctionsofplacentalalkalinephosphataseinvivousingalpptransgenicmice AT hsihsienlin evaluationoftheimmunologicalfunctionsofplacentalalkalinephosphataseinvivousingalpptransgenicmice |