Abstract
Little has been reported about the effects of different polysaccharides
on cytokine production from human monocytes. In this study, we show
that several well-defined polysaccharides, including polymers with
different sizes of beta1-4-linked D-mannuronic acid (poly-M, high-M
alginate, and M-blocks) and cellulose oxidized in the C-6 position,
induced human monocytes to produce tumor necrosis factor alpha (TNF-alpha).
Poly-M was the most efficient polysaccharide tested and, on a weight
basis, was approximately as efficient as lipopolysaccharide (LPS)
from Escherichia coli. TNF-alpha production was shown to depend strongly
on the molecular weights of poly-M and high-M alginate, with maximal
TNF-alpha. production occurring at molecular weights above 50,000
and 200,000, respectively. G-blocks, alpha1-4-linked L-guluronic
acid polymers that did not induce cytokine production from monocytes,
reduced the cytokine production induced by the beta1-4-linked polyuronic
acids and LPS. Furthermore, both G-blocks and LPS were found to inhibit
the binding of poly-M to monocytes, as measured by flow cytometry.
In addition, we found that the binding of LPS to monocytes was inhibited
by G-blocks, M-blocks, and poly-M. Our results indicate that beta1-4-linked
polyuronic acids and LPS may stimulate monocytes to produce TNF-alpha
by similar mechanisms and may bind to a common receptor.
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