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2014 ; 35
(ä): 162-73
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Reprint of: A rapid increase in macrophage-derived versican and hyaluronan in
infectious lung disease
#MMPMID24727035
Chang MY
; Tanino Y
; Vidova V
; Kinsella MG
; Chan CK
; Johnson PY
; Wight TN
; Frevert CW
Matrix Biol
2014[Apr]; 35
(ä): 162-73
PMID24727035
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The goals of this study were to characterize the changes in chondroitin sulfate
proteoglycans and hyaluronan in lungs in acute response to gram-negative
bacterial infection and to identify cellular components responsible for these
changes. Mice were treated with intratracheal (IT) live Escherichia coli, E. coli
lipopolysaccharide (LPS), or PBS. Both E. coli and LPS caused rapid selective
increases in mRNA expression of versican and hyaluronan synthase (Has) isoforms 1
and 2 associated with increased immunohistochemical and histochemical staining
for versican and hyaluronan in the lungs. Versican was associated with a subset
of alveolar macrophages. To examine whether macrophages contribute to versican
and hyaluronan accumulation, in vitro studies with primary cultures of bone
marrow-derived and alveolar macrophages were performed. Unstimulated macrophages
expressed very low levels of versican and hyaluronan synthase mRNA, with no
detectible versican protein or hyaluronan product. Stimulation with LPS caused
rapid increases in versican mRNA and protein, a rapid increase in Has1 mRNA, and
concomitant inhibition of hyaluronidases 1 and 2, the major hyaluronan degrading
enzymes. Hyaluronan could be detected following chloroquine pre-treatment,
indicating rapid turnover and degradation of hyaluronan by macrophages. In
addition, the effects of LPS, the M1 macrophage classical activation agonist,
were compared to those of IL-4/IL-13 or IL-10, the M2a and M2c alternative
activation agonists, respectively. Versican and Has1 increased only in response
to M1 activation. Finally, the up-regulation of versican and Has1 in the whole
lungs of wild-type mice following IT LPS was completely abrogated in TLR-4(-/-)
mice. These findings suggest that versican and hyaluronan synthesis may play an
important role in the innate immune response to gram-negative lung infection.
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