The timing and sequence of the major apoptosis associated event in thymocyte
| Autor: | Po-Chiang Chan, 詹博強 |
|---|---|
| Rok vydání: | 2016 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 104 Every single day billions of cells die inside our bodies, and need to be replaced with new and fresh ones. Most of the time, cell death is achieved through a programmed process called “apoptosis” that eliminates cells before they become overwhelming, and clears them in immunologically “silent” way so that they are efficiently recycled. The apoptosis process have been studied extensively in vitro and we know a lot about the biological pathways and molecular interactions. However, much of our knowledge of morphology or biological changes has been gained from fixed samples or cultured cells that lack intact biological complexity such as cytokine and growth factor interactions and intact tissue architecture in three dimensional space. Our goal is to characterize the timing and the sequence of the major apoptosis-associated events in situ such as: (a) caspase-3 activation – an early marker of apoptosis, (b) contact with the phagocytosing cell, (c) exposure of “eat-me” signal - phosphatidylserine. Using a variety of dynamic imaging methods, we found out that phagocytosis of apoptotic cells is dependent on caspase 3 activation. In addition, we discovered that the average time between first contact with phagocyte to engulfment increased from 8 minutes (in situ) to 18 min (in vitro, without phosphatidylserine blocking) minutes and to 50 min (in vitro with phosphatidylserine blocking), suggesting that phosphatidylserine is very important signal for phagocytosis, especially in situ. To our knowledge this is the first dynamic assessment of the timing and sequence of apoptosis-associated events and this knowledge may give us an opportunity to elucidate the mechanism of cell death and clearance that could have therapeutic potential for treatment of autoimmune and inflammatory diseases. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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