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

Paulo N. Rocha, Troy J. Plumb, Lisa A. Robinson, Robert Spurney, David Pisetsky, Beverly H. Koller, Thomas M. Coffman

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)896-903
Number of pages8
JournalClinical and diagnostic laboratory immunology
Volume12
Issue number8
StatePublished - Aug 2005

    Fingerprint

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Clinical Biochemistry
  • Microbiology (medical)

Cite this

Rocha, P. N., Plumb, T. J., Robinson, L. A., Spurney, R., Pisetsky, D., Koller, B. H., & Coffman, T. M. (2005). Role of thromboxane A2 in the induction of apoptosis of immature thymocytes by lipopolysaccharide. Clinical and diagnostic laboratory immunology, 12(8), 896-903.