| ABBREVATIONS | 第1-11页 |
| ABSTRACT | 第11-13页 |
| 1 INTRODUCTION | 第13-35页 |
| ·Lymphocyte-mediated cytotoxicity | 第13-17页 |
| ·Two pathways of lymphocyte-mediated killing | 第13-16页 |
| ·CD8+ T cells and chemokines | 第16-17页 |
| ·Clearance of apoptotic cells | 第17-22页 |
| ·Clearance of apoptotic bodies | 第18-20页 |
| ·Suppression of inflammation | 第20-22页 |
| ·RANTES/CCL5 | 第22-30页 |
| ·Structure | 第23-25页 |
| ·Binding mechanism | 第25-27页 |
| ·Inhibition | 第27页 |
| ·Function | 第27-30页 |
| ·Protein painting of cell surfaces | 第30-32页 |
| ·Aims of the present study | 第32-35页 |
| 2 MATERIALS AND METHODS | 第35-58页 |
| ·Materials | 第35-46页 |
| ·Chemicals | 第35-38页 |
| ·Buffers and Solutions | 第38-41页 |
| ·Reaction systems | 第41-42页 |
| ·Recombinant chemokines | 第42页 |
| ·Monoclonal Antibodies | 第42-43页 |
| ·Cell lines | 第43页 |
| ·Chinese hamster ovary (CHO) cells | 第43页 |
| ·Colon 26 cells | 第43页 |
| ·Animals | 第43页 |
| ·Primers for amplification and mutation | 第43-44页 |
| ·Apparatuses used in this work | 第44-46页 |
| ·Methods | 第46-58页 |
| ·Cell culture | 第47页 |
| ·Plasmid construction | 第47-50页 |
| ·Construction of PEF/RANTES-LFA3 | 第47-49页 |
| ·Construction of RANTES mutants | 第49-50页 |
| ·Electroporation into CHO cells | 第50-52页 |
| ·Preparation of DNA for stable transfection | 第50-51页 |
| ·Preparation of the cells for electroporation | 第51页 |
| ·Electroporate the cells | 第51页 |
| ·Culture of transfected cells | 第51-52页 |
| ·Detection of surface expressed RANTES-GPI | 第52-54页 |
| ·Flow cytometric analysis | 第52页 |
| ·Immunofluorescence staining | 第52-53页 |
| ·Immunogold electron microscopy | 第53-54页 |
| ·Assessment of RANTES-stimulated Mφ phagocytosis in vitro | 第54-56页 |
| ·Induction of apoptosis | 第54页 |
| ·Labelling of apoptotic bodies | 第54页 |
| ·Detection of surface-bound RANTES by flow cytometry | 第54-55页 |
| ·Isolation of murine peritoneal macrophages | 第55页 |
| ·Phagocytosis assay by flow cytometry | 第55页 |
| ·Phagocytosis assay by cytology | 第55-56页 |
| ·Phagocytosis assay by electron microscopy | 第56页 |
| ·Inhibitor and antibody studies | 第56页 |
| ·Assessment of RANTES-stimulated Mφ phagocytosis in vivo | 第56-57页 |
| ·Statistical analysis | 第57-58页 |
| 3 RESULTS | 第58-80页 |
| ·Construction and expression of RANTES-GPI and RANTES mutants-GPI chimera | 第58-65页 |
| ·Construction of RANTES-GPI and RANTES mutants-GPI | 第58-63页 |
| ·Expression of RANTES-GPI and RANTES mutants-GPI | 第63-65页 |
| ·Fluorescence-activated cell sorting (FACS) analysis | 第63-64页 |
| ·Immunofluorescence staining | 第64页 |
| ·Immunogold labeling | 第64-65页 |
| ·Apoptosis induced by cycloheximide | 第65-66页 |
| ·RANTES binding to the surface of apoptotic Colon 26 and CHO cells | 第66-68页 |
| ·Ultrastructural feastures of uptake of apoptotic bodies | 第68-69页 |
| ·RANTES stimulate Mφ phagocytosis of apoptotic cells | 第69-72页 |
| ·Met-RANTES does not stimulate Mφ phagocytosis of apoptotic bodies in vitro | 第72-74页 |
| ·Enhancement of Mφ phagocytosis of apoptotic bodies in vitro: A CCR1 dependent mechanism | 第74-76页 |
| ·Chondroitin sulfates block RANTES enhancement of Mφ phagocytosis | 第76-77页 |
| ·RANTES stimulates Mφ phagocytosis of exogenously administered apoptotic Colon 26 in vivo | 第77-78页 |
| ·Stimulation of Mφ phagocytosis of apoptotic cells is an unique role of RANTES among β-chemokines | 第78-80页 |
| 4 DISCUSSION | 第80-87页 |
| ·GPI-modified RANTES and its mutants | 第81页 |
| ·RANTES augmentation of Mφ capacity for phagocytosis of apoptotic cells | 第81-83页 |
| ·Aggregation of RANTES is responsible for augmentation of Mφ capacity | 第83-84页 |
| ·CCR1 is required for RANTES augmentation of Mφ capacity | 第84-86页 |
| ·Conclusions | 第86-87页 |
| 5 SUMMARY | 第87-91页 |
| 6 REFERENCES | 第91-102页 |
| 7 CURRICULUM VITAE | 第102-104页 |
| 8 SELECTED PUBLICATIONS | 第104-105页 |
| 9 ACKNOWLEDGMENTS | 第105页 |
