Paulo N Rocha, Troy J Plumb, Lisa A Robinson, Robert Spurney, David Pisetsky, Beverly H Koller, Thomas M Coffman
{"title":"血栓素A2在脂多糖诱导未成熟胸腺细胞凋亡中的作用。","authors":"Paulo N Rocha, Troy J Plumb, Lisa A Robinson, Robert Spurney, David Pisetsky, Beverly H Koller, Thomas M Coffman","doi":"10.1128/CDLI.12.8.896-903.2005","DOIUrl":null,"url":null,"abstract":"<p><p>Lipopolysaccharide (LPS) causes apoptotic deletion of CD4(+) CD8(+) thymocytes, a phenomenon that has been linked to immune dysfunction and poor survival during sepsis. Given the abundance of thromboxane-prostanoid (TP) receptors in CD4(+) CD8(+) thymocytes and in vitro evidence that thromboxane A(2) (TXA(2)) causes apoptosis of these cells, we tested whether enhanced generation of TXA(2) plays a role in LPS-induced thymocyte apoptosis. Mice injected with 50 micro LPS intraperitoneally displayed a marked increase in generation of TXA(2) and prostaglandin E(2) in the thymus as well as apoptotic deletion of CD4(+) CD8(+) thymocytes. Administration of indomethacin or rofecoxib inhibited prostanoid synthesis but did not affect thymocyte death. In contrast, thymocyte apoptosis in response to LPS was significantly attenuated in TP-deficient mice. These studies indicate that TXA(2) mediates a portion of apoptotic thymocyte death caused by LPS. The absence of an effect of global inhibition of prostanoid synthesis suggests a complex role for prostanoids in this model.</p>","PeriodicalId":72602,"journal":{"name":"Clinical and diagnostic laboratory immunology","volume":"12 8","pages":"896-903"},"PeriodicalIF":0.0000,"publicationDate":"2005-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1128/CDLI.12.8.896-903.2005","citationCount":"13","resultStr":"{\"title\":\"Role of thromboxane A2 in the induction of apoptosis of immature thymocytes by lipopolysaccharide.\",\"authors\":\"Paulo N Rocha, Troy J Plumb, Lisa A Robinson, Robert Spurney, David Pisetsky, Beverly H Koller, Thomas M Coffman\",\"doi\":\"10.1128/CDLI.12.8.896-903.2005\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Lipopolysaccharide (LPS) causes apoptotic deletion of CD4(+) CD8(+) thymocytes, a phenomenon that has been linked to immune dysfunction and poor survival during sepsis. Given the abundance of thromboxane-prostanoid (TP) receptors in CD4(+) CD8(+) thymocytes and in vitro evidence that thromboxane A(2) (TXA(2)) causes apoptosis of these cells, we tested whether enhanced generation of TXA(2) plays a role in LPS-induced thymocyte apoptosis. Mice injected with 50 micro LPS intraperitoneally displayed a marked increase in generation of TXA(2) and prostaglandin E(2) in the thymus as well as apoptotic deletion of CD4(+) CD8(+) thymocytes. Administration of indomethacin or rofecoxib inhibited prostanoid synthesis but did not affect thymocyte death. In contrast, thymocyte apoptosis in response to LPS was significantly attenuated in TP-deficient mice. These studies indicate that TXA(2) mediates a portion of apoptotic thymocyte death caused by LPS. The absence of an effect of global inhibition of prostanoid synthesis suggests a complex role for prostanoids in this model.</p>\",\"PeriodicalId\":72602,\"journal\":{\"name\":\"Clinical and diagnostic laboratory immunology\",\"volume\":\"12 8\",\"pages\":\"896-903\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2005-08-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://sci-hub-pdf.com/10.1128/CDLI.12.8.896-903.2005\",\"citationCount\":\"13\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Clinical and diagnostic laboratory immunology\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1128/CDLI.12.8.896-903.2005\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical and diagnostic laboratory immunology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1128/CDLI.12.8.896-903.2005","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
Role of thromboxane A2 in the induction of apoptosis of immature thymocytes by lipopolysaccharide.
Lipopolysaccharide (LPS) causes apoptotic deletion of CD4(+) CD8(+) thymocytes, a phenomenon that has been linked to immune dysfunction and poor survival during sepsis. Given the abundance of thromboxane-prostanoid (TP) receptors in CD4(+) CD8(+) thymocytes and in vitro evidence that thromboxane A(2) (TXA(2)) causes apoptosis of these cells, we tested whether enhanced generation of TXA(2) plays a role in LPS-induced thymocyte apoptosis. Mice injected with 50 micro LPS intraperitoneally displayed a marked increase in generation of TXA(2) and prostaglandin E(2) in the thymus as well as apoptotic deletion of CD4(+) CD8(+) thymocytes. Administration of indomethacin or rofecoxib inhibited prostanoid synthesis but did not affect thymocyte death. In contrast, thymocyte apoptosis in response to LPS was significantly attenuated in TP-deficient mice. These studies indicate that TXA(2) mediates a portion of apoptotic thymocyte death caused by LPS. The absence of an effect of global inhibition of prostanoid synthesis suggests a complex role for prostanoids in this model.