title: The CD95/CD95L pathway is involved in phagocytosis-induced cell death of monocytes and may account for sustained inflammation in neonates.
abstract: BACKGROUND
  The propensity for sustained inflammation after bacterial infection in neonates, resulting in inflammatory sequelae such as bronchopulmonary dysplasia and periventricular leucomalacia, is well known, but its molecular mechanisms remain elusive. Termination of inflammatory reactions physiologically occurs early after removal of bacteria by phagocytosis-induced cell death (PICD) of immune effector cells such as monocytes. PICD from cord blood monocytes (CBMOs) was shown to be reduced as compared with that of peripheral blood monocytes (PBMOs) from adult donors in vitro.
  
  
  METHODS
  PBMOs, CBMOs, and Fas (CD95)-deficient (lpr) mouse monocytes were analyzed in an in vitro infection model using green fluorescence protein-labeled Escherichia coli (E. coli-GFP). Phagocytosis and apoptosis were quantified by flow cytometry and CD95L secretion was quantified by enzyme-linked immunosorbent assay.
  
  
  RESULTS
  We demonstrate the involvement of the CD95/CD95 ligand pathway (CD95/CD95L) in PICD and provide evidence that diminished CD95L secretion by CBMOs may result in prolonged activation of neonatal immune effector cells.
  
  
  CONCLUSIONS
  These in vitro results offer for the first time a molecular mechanism accounting for sustained inflammation seen in neonates.
authors.affiliation: Department of Neonatology, University Children's Hospital, Tuebingen, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Gille
authors.forename: Stephan
authors.initials: S
authors.lastname: Dreschers
authors.forename: Anja
authors.initials: A
authors.lastname: Leiber
authors.forename: Florian
authors.initials: F
authors.lastname: Lepiorz
authors.forename: Matthias
authors.initials: M
authors.lastname: Krusch
authors.forename: Julia
authors.initials: J
authors.lastname: Grosse-Opphoff
authors.forename: Bärbel
authors.initials: B
authors.lastname: Spring
authors.forename: Martin
authors.initials: M
authors.lastname: Haas
authors.forename: Michael
authors.initials: M
authors.lastname: Urschitz
authors.forename: Christian F
authors.initials: CF
authors.lastname: Poets
authors.forename: Thorsten W
authors.initials: TW
authors.lastname: Orlikowsky
mesh_terms: D000328:Adult; D000818:Animals; D017209:Apoptosis; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity; D053222:Fas Ligand Protein / Q000378:metabolism*; D005312:Fetal Blood / Q000276:immunology*; D005434:Flow Cytometry; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D007231:Infant, Newborn; D007249:Inflammation / Q000097:blood / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D010587:Phagocytosis; D015398:Signal Transduction; D019014:fas Receptor / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: D017077:Culture Media, Conditioned; C491901:FAS protein, human; C505661:FASLG protein, human; D053222:Fas Ligand Protein; C491899:Fas protein, mouse; C505658:Fasl protein, mouse; D019014:fas Receptor; D049452:Green Fluorescent Proteins