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*
Department of Dermatology, University of Freiburg, Freiburg, Germany; and
Department of Biochemistry, University of Munster, Munster, Germany
The extracellular matrix component hyaluronan (HA) exists
physiologically as a high m.w. polymer but is cleaved at sites of
inflammation, where it will be contacted by dendritic cells (DC). To
determine the effects of HA on DC, HA fragments of different size were
established. Only small HA fragments of tetra- and hexasaccharide size
(sHA), but not of intermediate size (m.w. 80,000–200,000) or high m.w.
HA (m.w. 1,000,000–600,000) induced immunophenotypic maturation of
human monocyte-derived DC (up-regulation of HLA-DR, B7-1/2, CD83,
down-regulation of CD115). Likewise, only sHA increased DC production
of the cytokines IL-1ß, TNF-
, and IL-12 as well as their
allostimulatory capacity. These effects were highly specific for sHA,
because they were not induced by other glycosaminoglycans such as
chondroitin sulfate or heparan sulfate or their fragmentation products.
Interestingly, sHA-induced DC maturation does not involve the HA
receptors CD44 or the receptor for hyaluronan-mediated motility,
because DC from CD44-deficient mice and wild-type mice both responded
similarly to sHA stimulation, whereas the receptor for
hyaluronan-mediated motility is not detectable in DC. However, TNF-
is an essential mediator of sHA-induced DC maturation as shown by
blocking studies with a soluble TNFR1. These findings suggest that
during inflammation, interaction of DC with small HA fragments induce
DC maturation.
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