Interaction of lactoferrin and lipopolysaccharide (LPS): effects on the antioxidant property of lactoferrin and the ability of LPS to prime human neutrophils for enhanced superoxide formation.
Lactoferrin is a 77-kDa iron-binding protein to which a wide variety of divergent biologic functions have been ascribed. It has recently been reported that lactoferrin interacts with bacterial lipopolysaccharide (LPS) in such a fashion as to affect the binding of lactoferrin to myeloid cells. Two other potential interactions of LPS and lactoferrin were explored. Lactoferrin prevents hydroxyl radical formation by binding iron, even at low pH. Lactoferrin inhibited iron-catalyzed formation of hydroxyl radical in the presence of LPS at pH 7.4 and 4.5. Low concentrations of LPS can be used to "prime" neutrophils toward enhanced function, such as formation of stimulated superoxide anion. Lactoferrin inhibited LPS priming of neutrophils if LPS contamination of the protein (provided by commercial suppliers) was first reduced. Inhibition of LPS priming was observed whether apolactoferrin or iron-saturated lactoferrin was used. Similar inhibition of LPS priming was observed when neutrophils were incubated with other serum proteins (e.g., albumin, apotransferrin, or iron-saturated transferrin). These results show that LPS should not be expected to affect the free radical biology of lactoferrin, which is a crucial physiologic function of this protein. However, lactoferrin inhibits LPS priming, and this effect requires consideration in experimental models of inflammation.
Cohen
M S
MS
Department of Internal Medicine, University of North Carolina, Chapel Hill 27599-7030.
Mao
J
J
Rasmussen
G T
GT
Serody
J S
JS
Britigan
B E
BE
D001059:Apoproteins / Q000378:metabolism; D002478:Cells, Cultured; D006801:Humans; D007781:Lactoferrin / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000378:metabolism*; D009504:Neutrophils / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism*
D001059:Apoproteins; D008070:Lipopolysaccharides; C039223:apolactoferrin; D013481:Superoxides; D007781:Lactoferrin