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A membrane-type surfactant protein D (SP-D) suppresses macrophage-mediated cytotoxicity in swine endothelial cells
- Source :
- Transplant Immunology. 47:44-48
- Publication Year :
- 2018
- Publisher :
- Elsevier BV, 2018.
-
Abstract
- Objective Surfactant protein D (SP-D), which is secreted mainly in the lung, is an oligometric C type lectin that promotes phagocytosis by binding to carbohydrates on microbial surfaces. SP-D can also bind SIRPα, leading to a decrease in cytokine production by monocytes/macrophages. In the present study, we examined the possibility that SP-D suppresses macrophage-mediated xenogeneic cytotoxicity, by creating a membrane-type SP-D. Methods The cDNA for the carbohydrate recognition domain (CRD) of human SP-D was switched to that of a membrane-type protein, collectin placenta 1 (CL-P1), with a Flag-tag. The cDNA of CD47 was prepared as a control. The suppressive function of the membrane-type protein of the hybrid molecule, CL-SP-D, to monocytes/macrophages was then studied and the results compared with that for CD47. Results The expression of Flag-tagged CL-SP-D on the transfected SECs and the SIRPα on monocyte-like cells, THP-1 cells, was confirmed by FACS using anti-Flag Ab and anti-CD172a, respectively. The molecular size of the hybrid protein was next assessed by western blot. While significant cytotoxicity against SEC was induced in differentiated THP-1 cells, CL-SP-D significantly reduced THP-1-mediated cytotoxicity. In addition, phosphorylated SHP-1 was clearly detected in SEC/CL-SP-D in western blots. Moreover, IL-10 production was upregulated and IL-1β production was suppressed in the case of THP-1 and SEC/CL-SP-D, compared with naive SEC. Next, the cytotoxicity caused by the in vitro generated macrophage was assessed under the same conditions as were used for THP-1. CL-SP-D also showed the significant down-regulation on the macrophage. In addition, changes in IL-10 production by the macrophage confirmed the results. Conclusions These findings indicate that the membrane-type SP-D serve as an effective therapeutic strategy for inhibiting macrophage-mediated xenograft rejection in xenotransplantation.
- Subjects :
- Cytotoxicity, Immunologic
Graft Rejection
0301 basic medicine
Swine
THP-1 Cells
medicine.medical_treatment
Transplantation, Heterologous
Immunology
Collectin
03 medical and health sciences
Phagocytosis
Western blot
C-type lectin
Antigens, Heterophile
medicine
Animals
Humans
Immunology and Allergy
Macrophage
Receptors, Immunologic
Cytotoxicity
Lung
Cells, Cultured
Receptors, Scavenger
Transplantation
medicine.diagnostic_test
Chemistry
Macrophages
CD47
Endothelial Cells
Surfactant protein D
Pulmonary Surfactant-Associated Protein D
Antigens, Differentiation
Molecular biology
Collectins
Interleukin-10
Biological Therapy
030104 developmental biology
Cytokine
Subjects
Details
- ISSN :
- 09663274
- Volume :
- 47
- Database :
- OpenAIRE
- Journal :
- Transplant Immunology
- Accession number :
- edsair.doi.dedup.....8f31f6bd216a7b2a3f99684f28bd6bcc