title: Stimulus-dependent impairment of the neutrophil oxidative burst response in lactoferrin-deficient mice.
abstract: Lactoferrin (LF) is an iron-binding protein found in milk, mucosal secretions, and the secondary granules of neutrophils in which it is considered to be an important factor in the innate immune response against microbial infections. Moreover, LF deficiency in the secondary granules of neutrophils has long been speculated to contribute directly to the hypersusceptibility of specific granule deficiency (SGD) patients to severe, life-threatening bacterial infections. However, the exact physiological significance of LF in neutrophil-mediated host defense mechanisms remains controversial and has not yet been clearly established in vivo using relevant animal models. In this study, we used lactoferrin knockout (LFKO) mice to directly address the selective role of LF in the host defense response of neutrophils and to determine its contribution, if any, to the phenotype of SGD. Neutrophil maturation, migration, phagocytosis, granule release, and antimicrobial response to bacterial challenge were unaffected in LFKO mice. Interestingly, a stimulus-dependent defect in the oxidative burst response of LFKO neutrophils was observed in that normal activation was seen in response to opsonized bacteria whereas an impaired response was evident after phorbol myristate-13-acetate stimulation. Taken together, these results indicate that although LF deficiency alone is not a primary cause of the defects associated with SGD, this protein does play an immunomodulatory role in the oxidative burst response of neutrophils.
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
authors.forename: Pauline P
authors.initials: PP
authors.lastname: Ward
authors.forename: Marisela
authors.initials: M
authors.lastname: Mendoza-Meneses
authors.forename: Pyong W
authors.initials: PW
authors.lastname: Park
authors.forename: Orla M
authors.initials: OM
authors.lastname: Conneely
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D004198:Disease Susceptibility / Q000276:immunology / Q000382:microbiology; D004306:Dose-Response Relationship, Immunologic; D007781:Lactoferrin / Q000172:deficiency*; D007962:Leukocytes / Q000187:drug effects / Q000382:microbiology; D008168:Lung / Q000187:drug effects / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019255:NADPH Oxidases / Q000378:metabolism; D009504:Neutrophils / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism* / Q000382:microbiology; D009195:Peroxidase / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000502:physiology; D016897:Respiratory Burst / Q000187:drug effects / Q000276:immunology*; D022142:Secretory Vesicles / Q000378:metabolism; D013211:Staphylococcus aureus / Q000187:drug effects / Q000502:physiology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D009195:Peroxidase; D019255:NADPH Oxidases; D007781:Lactoferrin; D013755:Tetradecanoylphorbol Acetate