The impact of hyaluronan on monocyte Toll-like receptor expression in term infant cord blood

Authors

  • Helene CD Østerholt,

    1. .Department of Pediatrics, Akershus University Hospital, Lørenskog, Norway
    2. .Department of Pediatric Research, Rikshospitalet, Oslo University Hospital, Oslo, Norway
    3. .Institute of Clinical Medicine, University of Oslo, Oslo, Norway
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  • Bård Lundeland,

    1. .Institute of Clinical Medicine, University of Oslo, Oslo, Norway
    2. .Department of Anesthesiology, Akershus University Hospital, Lørenskog, Norway
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  • Tonje Sonerud,

    1. .Department of Pediatrics, Akershus University Hospital, Lørenskog, Norway
    2. .Department of Clinical Molecular Biology and Laboratory Sciences (EpiGen), Akershus University Hospital, University of Oslo, Oslo, Norway
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  • Ola D Saugstad,

    1. .Department of Pediatric Research, Rikshospitalet, Oslo University Hospital, Oslo, Norway
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  • Britt Nakstad

    1. .Department of Pediatrics, Akershus University Hospital, Lørenskog, Norway
    2. .Institute of Clinical Medicine, University of Oslo, Oslo, Norway
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  • [Correction added after online publication April 12, 2012: Fig. 1 caption has been corrected].

HCD Østerholt, Department of Pediatrics, Akershus University Hospital, N-1478 Lørenskog, Norway.
Tel: +47 97524626 |
Email: helendo@medisin.uio.no

Abstract

Aim:  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.

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