title: The impact of hyaluronan on monocyte Toll-like receptor expression in term infant cord blood.
abstract: OBJECTIVE
  To explore the possible effects of hyaluronan, an endogenous mediator of inflammation, on monocyte surface expression of Toll-like receptors 2 and 4 in human umbilical cord blood ex vivo, and in a model mimicking Gram-negative neonatal sepsis.
  
  
  METHODS
  Term infant cord blood was obtained after elective caesarean sections, n = 15. Both unstimulated and lipopolysaccharide-stimulated (10 ng/mL) blood was incubated with 500 μg/mL high- or low-molecular-weight hyaluronan for 6 h. Expression of Toll-like receptors 2 and 4 on monocytes was measured using flow cytometry, and plasma concentrations of proinflammatory cytokines and matrix metalloproteinase 9 were analysed. RESULTS (MEAN ± SEM): We found a significant decrease in Toll-like receptor 4 expression in the presence of high-molecular-weight hyaluronan (HMW HA) in unstimulated blood (median fluorescence intensity 141 ± 7.3 vs. 163 ± 9.8, p = 0.019). There were no significant changes in Toll-like receptor 2 expression. Levels of cytokines and matrix metalloproteinase 9 increased in the presence of both forms of hyaluronan.
  
  
  CONCLUSIONS
  Our results confirm that hyaluronan affects the neonatal immune response. The biological significance of these findings requires further clarification. More studies are needed to validate the possible down-modulation of Toll-like receptor 4 exerted by HMW HA.
authors.affiliation: Department of Pediatrics, Akershus University Hospital, Lørenskog, Norway. helendo@medisin.uio.no
authors.forename: Helene C D
authors.initials: HC
authors.lastname: Osterholt
authors.forename: Bård
authors.initials: B
authors.lastname: Lundeland
authors.forename: Tonje
authors.initials: T
authors.lastname: Sonerud
authors.forename: Ola D
authors.initials: OD
authors.lastname: Saugstad
authors.forename: Britt
authors.initials: B
authors.lastname: Nakstad
mesh_terms: D015415:Biomarkers / Q000097:blood; D016207:Cytokines / Q000097:blood; D005312:Fetal Blood / Q000276:immunology* / Q000378:metabolism; D005434:Flow Cytometry; D016905:Gram-Negative Bacterial Infections / Q000276:immunology*; D006801:Humans; D006820:Hyaluronic Acid / Q000276:immunology*; D066298:In Vitro Techniques; D007231:Infant, Newborn; D008070:Lipopolysaccharides; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D009000:Monocytes / Q000378:metabolism*; D018805:Sepsis / Q000276:immunology*; D051195:Toll-Like Receptor 2 / Q000097:blood*; D051197:Toll-Like Receptor 4 / Q000097:blood*
chemical_list: D015415:Biomarkers; D016207:Cytokines; D008070:Lipopolysaccharides; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; C440499:lipopolysaccharide, Escherichia coli O111 B4; D006820:Hyaluronic Acid; D020780:Matrix Metalloproteinase 9