title: An expanding role for apolipoprotein E in sepsis and inflammation.
abstract: BACKGROUND
  Apolipoprotein E (apoE), a component of plasma lipoproteins, plays an important, but poorly defined role in sepsis. We have shown that injecting apoE increases septic mortality in a rat model of gram-negative bacterial sepsis, with concomitant hepatic natural killer T (NKT) cell proliferation and activation. The presumed mechanism for this apoE-mediated mortality is that apoE can bind and traffic antigens, presumed to include lipopolysaccharide (LPS), and promote activation of dendritic cells (DC) with subsequent NKT activation and cytokine release. Thus, we sought to prove that LPS was the antigen responsible for the increased NKT activation enhanced by the presence of apoE.
  
  
  METHODS
  We isolated murine marrow-derived DCs, pulsed them with lipid antigen (LPS, and positive controls alpha-galactosylceramide [alpha-GalCer] and isoglobotrihexosylceramide 3 [iGb3]) with or without apoE, and then cocultured the DCs with hybridoma NKTs. NKT activation was measured by interleukin-2 (IL-2) supernatant levels using enzyme-linked immunosorbent assay (ELISA).
  
  
  RESULTS
  LPS at different concentrations was a weak stimulus for NKT activation regardless of apoE presence. When apoE was present, iGb3, an endogenous ligand analog, elicited more than a 2-fold increase in IL-2 response when compared with iGb3 alone (P < .05).
  
  
  CONCLUSIONS
  These results indicate an endogenous ligand, not LPS, may be responsible for NKT activation. A molecular remnant similar to iGb3 could act as a damage-associated molecular pattern and play a prominent role in animal models of sepsis.
authors.affiliation: Department of Surgery, University of California, San Francisco, East Bay, Oakland, USA.
authors.forename: Kelley
authors.initials: K
authors.lastname: Chuang
authors.forename: Erica L
authors.initials: EL
authors.lastname: Elford
authors.forename: Jill
authors.initials: J
authors.lastname: Tseng
authors.forename: Briana
authors.initials: B
authors.lastname: Leung
authors.forename: Hobart W
authors.initials: HW
authors.lastname: Harris
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D005915:Globosides / Q000276:immunology; D016905:Gram-Negative Bacterial Infections / Q000276:immunology / Q000401:mortality*; D022781:Hepatocytes / Q000187:drug effects / Q000276:immunology; D007249:Inflammation / Q000276:immunology / Q000401:mortality; D007376:Interleukin-2 / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology; D051381:Rats; D018805:Sepsis / Q000276:immunology / Q000401:mortality*; D014281:Trihexosylceramides / Q000276:immunology
chemical_list: D001057:Apolipoproteins E; D005915:Globosides; D007376:Interleukin-2; D014281:Trihexosylceramides; C514781:isoglobotrihexosylceramide
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