title: Role of thromboxane A2 in the induction of apoptosis of immature thymocytes by lipopolysaccharide.
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.
authors.affiliation: Division of Nephrology, Duke University, Durham VA Medical Centers, Durham, North Carolina 27705, USA.
authors.forename: Paulo N
authors.initials: PN
authors.lastname: Rocha
authors.forename: Troy J
authors.initials: TJ
authors.lastname: Plumb
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Robinson
authors.forename: Robert
authors.initials: R
authors.lastname: Spurney
authors.forename: David
authors.initials: D
authors.lastname: Pisetsky
authors.forename: Beverly H
authors.initials: BH
authors.lastname: Koller
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Coffman
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011453:Prostaglandins / Q000096:biosynthesis; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors / Q000502:physiology*; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects*
chemical_list: D016861:Cyclooxygenase Inhibitors; D008070:Lipopolysaccharides; D011453:Prostaglandins; D013928:Thromboxane A2