– Lactoferrin
Protects Against by Makoto Yamaguchi,* Department of Nutritional
Research, Nutrition Science Institute, Received 13 February 2001/Returned
for modification BALB/c mice were
intravenously injected with lipopolysaccharide (LPS) (0.05 µg/g
of body weight) 7 days after being primed with zymosan.
Recombinant human lactoferrin (250 µg/g of body weight),
intravenously administered 1 day before the injection of
LPS, significantly lessened the severity of hepatitis,
as assessed by levels of serum alanine transaminase compared
to those seen when casein was administered. The transient
rise of serum tumor necrosis factor alpha (TNF-alpha )
after LPS treatment was also significantly lowered by the
intravenous administration of lactoferrin, suggesting that
the effect of lactoferrin was due to the suppression of
TNF-alpha production. The following results indicate that
the sites of action of lactoferrin for the suppression
of the development of this type of hepatitis are Kupffer
cells. Gadolinium chloride, a substance known to eliminate
Kupffer cells, administered 1 day before LPS, inhibited
the transient rise of TNF-alpha and protected against the
development of hepatitis. Kupffer cells isolated from mice
intraperitoneally injected with recombinant human lactoferrin
became refractory to LPS. The specific interaction of recombinant
human lactoferrin with the Kupffer cells was shown by a
binding assay, which revealed two types of binding sites
on mouse Kupffer cells. Of the two dissociation constants
determined in this way, the lower dissociation constant,
0.47 × 10-6 M, was within the range of the 50% effective
doses for the suppression of TNF-alpha production. These
results suggest that recombinant human lactoferrin administered
to mice suppresses the production of TNF-alpha by Kupffer
cells by directly associating with the binding sites on
these cells. For more information on Lactoferrin,
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