Abstract
Apoptotic macrophages are removed by neighboring phagocytes (efferocytosis), which is an important event in advanced atherosclerosis. Recent reports have elucidated some key molecular regulators in efferocytosis including complement C1q, MFGE8, and MERTK. However, it remains unknown whether the long pentraxin 3 (PTX3), which is an important molecule that is involved in apoptotic cell clearance in the immune response, plays a part in efferocytosis during advanced atherosclerosis. In this study, we modeled macrophage apoptosis in advanced plaques by incubating macrophages (peritoneal macrophages isolated from C57 mice) with free cholesterol (free cholesterol-induced apoptotic macrophages, FC-AMs). FC-AMs were added to a monolayer of fresh phagocytes to study the engulfment response. We observed that PTX3 was mainly located at the membrane of late apoptotic macrophages. The anti-PTX3 monoclonal Ab 16B5 inhibited the engulfment of late apoptotic macrophages by phagocytes in a dose-dependent manner (from 14.63% inhibition at 5 μg/ml to 26.19% inhibition at 50 μg/ml). These results suggest that PTX3 located at the membrane of late apoptotic macrophages mediates their phagocytosis by phagocytes in a cell model of advanced atherosclerosis.
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Abbreviations
- MFGE8:
-
Milk fat globulin E8
- MERTK:
-
MER tyrosine kinase
- FC-AMs:
-
Free cholesterol-induced apoptotic macrophages
- PTX3:
-
Pentraxin 3
- CRP:
-
C-reactive protein
- SAP:
-
Serum amyloid-P
- DCs:
-
Dendritic cells
- CVD:
-
Cardiovascular disease
- GAS6:
-
Growth arrest-specific protein 6
- DMEM:
-
Dulbecco’s modified Eagle’s medium
- ACAT:
-
Acyl-CoA:cholesterol O-acyltransferase
- NECDS:
-
Non-enzymatic cell dissociation solution
- PBS:
-
Phosphate-buffered saline
- UV-AMs:
-
Ultraviolet-induced apoptotic macrophages
- FACS:
-
Fluorescence-activated cell sorter
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Acknowledgments
This research was supported by grants from the National Natural Science Foundation of P. R. China (No. 30471921). We thank our teacher, Jianfang Zhu, from the Laboratory of Human Genome Research at Union Hospital for providing the experimental platform. We sincerely acknowledge Professor Ira Tabas for his advice concerning the experiment methods.
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Tangmeng Guo and Li Ke contributed equally to this study.
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Guo, T., Ke, L., Qi, B. et al. PTX3 Is Located at the Membrane of Late Apoptotic Macrophages and Mediates the Phagocytosis of Macrophages. J Clin Immunol 32, 330–339 (2012). https://doi.org/10.1007/s10875-011-9615-6
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DOI: https://doi.org/10.1007/s10875-011-9615-6