Open AccessRole of Thromboxane A2in the Induction of Apoptosis of Immature Thymocytes by Lipopolysaccharide
Author(s) -
Paulo Novis Rocha,
Troy J. Plumb,
Lisa A. Robinson,
Robert F. Spurney,
David S. Pisetsky,
Beverly H. Koller,
Thomas M. Coffman
Publication year - 2005
Publication title -
clinical and vaccine immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.649
H-Index - 77
eISSN - 1556-6811
pISSN - 1556-679X
DOI - 10.1128/cdli.12.8.896-903.2005
Subject(s) - thymocyte , cd8 , apoptosis , prostanoid , lipopolysaccharide , thromboxane , thromboxane b2 , endocrinology , thromboxane a2 , medicine , biology , fas ligand , prostaglandin , immune system , eicosanoid , chemistry , programmed cell death , immunology , receptor , biochemistry , platelet , arachidonic acid , enzyme
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.