Journal of Leukocyte Biology
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Originally published online as doi:10.1189/jlb.1106688 on May 2, 2007

Published online before print May 2, 2007
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(Journal of Leukocyte Biology. 2007;82:347-353.)
© 2007 by Society for Leukocyte Biology

Role of endogenous interferon and LPS in the immunomodulatory effects of bovine lactoferrin in murine peritoneal macrophages

Patrizia Puddu*, Maria Grazia Carollo*, Filippo Belardelli*, Piera Valenti{dagger} and Sandra Gessani*,1

* Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy; and
{dagger} Department of Experimental Medicine, II University of Naples, Naples, Italy

1 Correspondence: Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy. E-mail: sandra.gessani{at}iss.it

Lactoferrin (Lf) plays an important role in host defense against infection and excessive inflammation. Although the mechanisms underlying its immunomodulatory properties have not been fully elucidated yet, recent evidence suggests that some of these effects may be related to its capacity to form complexes with LPS. We report that the culture of resting mouse peritoneal macrophages (PM) with bovine Lf (bLf), prior to infection with the vesicular stomatitis virus (VSV), resulted in a significant reduction of virus yield with respect to control cultures. The antiviral activity of bLF was related to its capacity of inducing IFN-{alpha}/β expression, which in turn inhibited VSV replication. Indeed, the accumulation of IFN-β but not of IFN{alpha}1-2 transcripts was up-modulated markedly early after bLf addition. Furthermore, bLf did not exert any antiviral activity in the presence of neutralizing antibodies to IFN-{alpha}/β in PM from wild-type mice, as well as in PM from mice genetically defective for the response to IFN. The antiviral activity of bLf relied on its intrinsic capacity to bind LPS, as this protein did not induce IFN expression in PM from LPS-hyporesponsive mice. It is interesting that this LPS-binding property was dispensable for the production of TNF-{alpha}, which also occurred in LPS-hyporesponsive mice. Overall, these results indicate that some of the immunomodulatory effects ascribed to Lf may be related to its capacity to favor Type I IFN expression and argue in favor of an important role of the LPS-binding feature and TLR4 in some of the effects ascribed to this molecule.

Key Words: cytokines • vesicular stomatitis virus






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