Release of iron from phagocytosed Escherichia coli and uptake by neutrophil lactoferrin.
Escherichia coli were labeled with 59Fe and then either treated with myeloperoxidase, H2O2, and chloride or opsonized and mixed with human neutrophils. The myeloperoxidase system at pH 7.4 caused release of most of the bacterial 59Fe. A similar result has been obtained by Rosen and Klebanoff (J Biol Chem 257:13731, 1982) but at pH 5. Iron release at pH 7.4 did not require the presence of a chelator, and the majority passed through a 10,000 relative molecular mass cut-off ultrafiltration membrane. When iron-poor lactoferrin was present during incubation with myeloperoxidase, 88% of the released 59Fe was precipitated with anti-lactoferrin antiserum, indicating that it was lactoferrin-bound. When the bacteria were mixed with neutrophils in a 10:1 ratio, approximately 50% were phagocytosed. About 40% of the 59Fe was released from the ingested bacteria over a 40-minute period. Initially, most remained associated with the neutrophil phagosomes, but with time, there was gradual transfer of some of the iron to the medium. Using anti-lactoferrin antiserum, 50% to 60% of phagosomal iron and 64% to 71% of iron in the medium was shown to be bound to lactoferrin. Thus, iron is released from phagocytosed E coli. Most becomes bound to lactoferrin, and some of this is released into the surroundings of the neutrophils. This suggests that neutrophil lactoferrin may function to trap iron from ingested microorganisms, enabling its removal from sites of inflammation. This may prevent iron from catalyzing undesirable oxidative reactions, as well as making it unavailable for growth of microorganisms that survive the killing process.
Molloy
A L
AL
Department of Pathology, School of Medicine, Christchurch Hospital, New Zealand.
Winterbourn
C C
CC
D004926:Escherichia coli / Q000276:immunology*; D006801:Humans; D007501:Iron / Q000032:analysis / Q000378:metabolism* / Q000493:pharmacokinetics; D007781:Lactoferrin / Q000378:metabolism*; D007782:Lactoglobulins / Q000378:metabolism*; D009504:Neutrophils / Q000378:metabolism*; D009195:Peroxidase / Q000378:metabolism / Q000494:pharmacology; D010587:Phagocytosis
D007782:Lactoglobulins; D007501:Iron; D009195:Peroxidase; D007781:Lactoferrin