| Content Provider |
World Health Organization (WHO)-Global Index Medicus |
| Author |
Niu, Shuo Tremblay, Alexandra Zhang, Xiugen Liu, Yuan Paluszynski, John Liu, Ming Ha, Binh Lv, Zhiyuan Shi, Lei Li, Liangwei Bian, Zhen Zen, Ke |
| Description |
Author Affiliation: Lv Z ( School of Life Sciences, Nanjing University, Nanjing 210023, China); Bian Z ( School of Life Sciences, Nanjing University, Nanjing 210023, China); Shi L ( School of Life Sciences, Nanjing University, Nanjing 210023, China); Niu S ( Program of Cellular Biology and Immunology, Department of Biology, Georgia State University, Atlanta, GA 30303); Ha B ( Program of Cellular Biology and Immunology, Department of Biology, Georgia State University, Atlanta, GA 30303); Tremblay A ( Program of Cellular Biology and Immunology, Department of Biology, Georgia State University, Atlanta, GA 30303); Li L ( Program of Cellular Biology and Immunology, Department of Biology, Georgia State University, Atlanta, GA 30303); Zhang X ( Program of Cellular Biology and Immunology, Department of Biology, Georgia State University, Atlanta, GA 30303); Paluszynski J ( Program of Cellular Biology and Immunology, Department of Biology, Georgia State University, Atlanta, GA 30303); Liu M ( Program of Cellular Biology and Immunology, Department of Biology, Georgia State University, Atlanta, GA 30303); Zen K ( School of Life Sciences, Nanjing University, Nanjing 210023, China); Liu Y ( Program of Cellular Biology and Immunology, Department of Biology, Georgia State University, Atlanta, GA 30303) |
| Abstract |
CD47, a self recognition marker expressed on tissue cells, interacts with immunoreceptor SIRP expressed on the surface of macrophages to initiate inhibitory signaling that prevents macrophage phagocytosis of healthy host cells. Previous studies suggested that cells may lose surface CD47 during aging or apoptosis to enable phagocytic clearance. In the current study, we demonstrate that the level of cell surface CD47 is not decreased, but the distribution pattern of CD47 is altered, during apoptosis. On nonapoptotic cells, CD47 molecules are clustered in lipid rafts forming punctates on the surface, whereas on apoptotic cells, CD47 molecules are diffused on the cell surface following the disassembly of lipid rafts. We show that clustering of CD47 in lipid rafts provides a high binding avidity for cell surface CD47 to ligate macrophage SIRP , which also presents as clusters, and elicits SIRP -mediated inhibitory signaling that prevents phagocytosis. In contrast, dispersed CD47 on the apoptotic cell surface is associated with a significant reduction in the binding avidity to SIRP and a failure to trigger SIRP signal transduction. Disruption of plasma membrane lipid rafts with methyl-ß-cyclodextrin diffuses CD47 clusters, leading to a decrease in the cell binding avidity to SIRP and a concomitant increase in cells being engulfed by macrophages. Taken together, our study reveals that CD47 normally is clustered in lipid rafts on nonapoptotic cells but is diffused in the plasma membrane when apoptosis occurs; this transformation of CD47 greatly reduces the strength of CD47-SIRP engagement, resulting in the phagocytosis of apoptotic cells. |
| ISSN |
00221767 |
| e-ISSN |
15506606 |
| DOI |
10.4049/jimmunol.1401719 |
| Journal |
The Journal of Immunology |
| Issue Number |
2 |
| Volume Number |
195 |
| Language |
English |
| Publisher |
The American Association of Immunologists |
| Publisher Date |
2015-07-15 |
| Publisher Place |
United States |
| Access Restriction |
Open |
| Subject Keyword |
Antigens, Cd47 Immunology Antigens, Differentiation Apoptosis Radiation Effects Epithelial Cells Macrophages Receptors, Immunologic Animals Chemistry Genetics Drug Effects Binding Sites Cell Line, Tumor Cytology Fibroblasts Gene Expression Regulation Leukocytes, Mononuclear Membrane Microdomains Mice Mice, Inbred C57bl Phagocytosis Primary Cell Culture Protein Binding Protein Transport Signal Transduction Spleen Ultraviolet Rays Beta-cyclodextrins Pharmacology Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't Discipline Immunology |
| Content Type |
Text |
| Resource Type |
Article |
| Subject |
Immunology and Allergy Immunology |
