Role of thromboxane A2 in the induction of apoptosis of immature thymocytes by lipopolysaccharide.


Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Rocha, PN; Plumb, TJ; Robinson, LA; Spurney, R; Pisetsky, D; Koller, BH; Coffman, TM

Published Date

  • August 2005

Published In

Volume / Issue

  • 12 / 8

Start / End Page

  • 896 - 903

PubMed ID

  • 16085905

Pubmed Central ID

  • 16085905

International Standard Serial Number (ISSN)

  • 1071-412X

Digital Object Identifier (DOI)

  • 10.1128/CDLI.12.8.896-903.2005


  • eng

Conference Location

  • United States