title: Increased lymphoid tissue apoptosis in baboons with bacteremic shock.
abstract: The molecular mechanisms of immune cell apoptosis during sepsis remain unclear. Two young adult baboons (Papio sp.) received a lethal dose of live Escherichia coli and were sacrificed at either 16 (for animal welfare concerns) or 24 h post-septic shock. An additional baboon, which received no bacteria, served as a control. Necropsy was performed immediately with subsequent immunohistochemical staining of lymphoid tissue. Immunohistologic analysis of tissues from the septic baboons revealed marked systemic lymphocyte apoptosis occurring in all lymphoid tissues examined. Focally, pyknotic and karyorrhectic lymphocytes demonstrated activation of a mitochondrial-dependent cell death pathway (active caspase 9 and apoptosis-inducing factor). Other regions demonstrated apoptotic lymphocytes with activation of a death receptor-dependent cell pathway (Fas ligand). Thus, we have demonstrated for the first time in primates that overwhelming gram-negative bacteremia produces an early and profound lymphocyte death that occurs through multiple cell death pathways. Bacteremic shock in the baboon may be an appropriate model for studying experimental therapies aimed at blocking lymphocyte apoptosis because their response appears comparable to humans dying from sepsis.
authors.affiliation: Department of Surgery, University of Florida College of Medicine, Gainesville, Florida 32610, USA.
authors.forename: Philip A
authors.initials: PA
authors.lastname: Efron
authors.forename: Kevin
authors.initials: K
authors.lastname: Tinsley
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: Minnich
authors.forename: Victor
authors.initials: V
authors.lastname: Monterroso
authors.forename: J
authors.initials: J
authors.lastname: Wagner
authors.forename: Pierre
authors.initials: P
authors.lastname: Lainée
authors.forename: Katrien
authors.initials: K
authors.lastname: Lorré
authors.forename: Paul E
authors.initials: PE
authors.lastname: Swanson
authors.forename: Richard
authors.initials: R
authors.lastname: Hotchkiss
authors.forename: Lyle L
authors.initials: LL
authors.lastname: Moldawer
mesh_terms: D000818:Animals; D017209:Apoptosis; D016470:Bacteremia / Q000473:pathology*; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism; D004927:Escherichia coli Infections / Q000473:pathology; D008198:Lymph Nodes / Q000473:pathology; D008214:Lymphocytes / Q000473:pathology; D008221:Lymphoid Tissue / Q000378:metabolism / Q000473:pathology*; D010215:Papio; D012772:Shock, Septic / Q000473:pathology*; D013154:Spleen / Q000473:pathology
chemical_list: D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases