Journal
INNATE IMMUNITY
Volume 16, Issue 2, Pages 67-79Publisher
SAGE PUBLICATIONS LTD
DOI: 10.1177/1753425909105317
Keywords
Lactoferrin; oxidative stress; mitochondria; DNA damage
Categories
Funding
- National Institute of General Medical Sciences [1R41GM079810-01]
- NIAID [AI062885-01]
- NIEHS Center [0 06677]
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Lactoferrin is a non-heme iron-binding glycoprotein, produced by mucosal epithelial cells and granulocytes in most mammalian species. It is involved in regulation of immune responses, possesses anti-oxidant, anti-carcinogenic, anti-inflammatory properties, and provides protection against various microbial infections. In addition, lactoferrin has been implicated in protection against the development of insult-induced systemic inflammatory response syndrome (SIRS) and its progression into septic conditions in vivo. Here we show a potential mechanism by which lactoferrin lessens oxidative insult at the cellular and tissue levels after lipopolysaccharide (LPS) exposure. Lactoferrin pretreatment of cells decreased LPS-mediated oxidative insults in a dose-dependent manner. Lipopolysaccharide-induced oxidative burst was found to be of mitochondrial origin, and release of reactive oxygen species (ROS) was localized to the respiratory complex III. Importantly, lactoferrin nearly abolished LPS-induced increases in mitochondrial ROS generation and the accumulation of oxidative damage in the DNA. In vivo, pretreatment of experimental animals with lactoferrin significantly (P50.05) lowered LPS-induced mitochondrial dysfunction as shown by both decreased release of H2O2 and DNA damage in the mitochondria. In contrast, deferoxamine, an iron chelating compound, provided only partial protection in LPS-treated animals. Together, these data suggest that lactoferrin protects against oxidative insult at the mitochondrial level, and indicate a potential utility of lactoferrin in prevention and treatment of SIRS.
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