1. Modeling The Early Events of Severe Acute Respiratory Syndrome Coronavirus Infection in Vitro2. Mechanistic Study of the Immunopathogenesis of Hemorrhage in a Dengue Mouse Model

• Main Authors: Yu-Ting Yen, 嚴玉婷
• Other Authors: Betty A. Wu-Hsieh
• Format: Others
• Language: zh-TW
• Published: 2009
• Online Access: http://ndltd.ncl.edu.tw/handle/27643812775576520717

博士 === 國立臺灣大學 === 免疫學研究所 === 97 === The clinical picture of SARS is characterized by pulmonary inflammation and respiratory failure, resembling that of ARDS. However, the events that lead to the recruitment of leukocytes are poorly understood. To study the cellular response in the acute phase of SARS-CoV-host cell interaction, we investigated the induction of chemokines, adhesion molecules and DC-SIGN by SARS-CoV. Immunohistochemistry analysis of autopsiyed specimens revealed neutrophil, macrophage and CD8 T cell infiltration in the lungs of a SARS patient who died during the acute phase of the illness. Additionally, pneumocytes and macrophages in the patient’s lung expressed P-selectin and DC-SIGN. In in vitro study, we showed that A549 and THP-1 cell lines were susceptible to SARS-CoV. A549 cells produced CCL2/MCP-1 and CXCL8/IL-8 after interaction with SARS-CoV and expressed P-selectin and VCAM-1. Moreover, SARS-CoV induced THP-1 cells to express CCL2/MCP-1, CXCL8/IL-8, CCL3/MIP-1, CXCL10/IP-10, CCL4/MIP-1 and CCL5/RANTES that attracted neutrophils, monocytes and activated T cells in a chemotaxis assay. We also demonstrated that DC-SIGN was inducible in THP-1 as well as A549 cells after SARS-CoV infection. Based on our results, we proposed that there are two waves of cell migration during the acute phase of SARS: (i) Pulmonary epithelial cells infected by SARS-CoV express adhesion molecules, upregulate DC-SIGN and produce CCL2/MCP-1 and CXCL8/IL-8 which are conducive for the recruitment of monocytes and neutrophils. (ii) The recruited monocytes interacting with SARS-CoV produce chemokines that attract a second wave of cells including neutrophils, activated T cells and more monocytes. The production of CCL2/MCP-1 by epithelial cells is key to the migration of two waves of cells.