title: Recombinant human lactoferrin modulates human PBMC derived macrophage responses to BCG and LPS.
abstract: Lactoferrin, an iron-binding glycoprotein found in mammalian mucosal secretions and granules of neutrophils, possesses several immune modulatory properties. Published reports indicate that lactoferrin enhances the efficacy of the tuberculosis vaccine, BCG (Bacillus Calmette Guerin), both by increasing macrophage and dendritic cell ability to stimulate receptive T cells and by modulating the inflammatory response. This report is the first to demonstrate the effects of a recombinant human lactoferrin (10 μg/mL) on human PBMC derived CD14+and CD16+macrophages stimulated with a strong (LPS, 10 ng/mL) or weaker (BCG, MOI 1:1) stimulator of inflammation. After 3 days culture, LPS and human lactoferrin treated CD14+cells significantly increased production of IL-10, IL-6, and MCP-1 compared to the LPS only group. In contrast, similarly treated CD16+macrophages increased production of IL-12p40 and IL-10 and decreased TNF-α. Limited changes were observed in BCG stimulated CD14+and CD16+macrophages with and without lactoferrin. Analysis of surface expression of antigen presentation and co-stimulatory molecules demonstrated that CD14+macrophages, when stimulated with BCG or LPS and cultured with lactoferrin, increased expression of CD86. CD16+macrophages treated with lactoferrin showed a similar trend of increase in CD86 expression, but only when stimulated with BCG.
authors.affiliation: Department of Pathology and Laboratory Medicine, UTHealth McGovern Medical School, Houston, TX, USA.
authors.forename: Shen-An
authors.initials: SA
authors.lastname: Hwang
authors.affiliation: Department of Integrative Biology and Pharmacology, UTHealth McGovern Medical School, Houston, TX, USA.
authors.forename: Marian L
authors.initials: ML
authors.lastname: Kruzel
authors.affiliation: Department of Pathology and Laboratory Medicine, UTHealth McGovern Medical School, Houston, TX, USA. Electronic address: Jeffrey.K.Actor@uth.tmc.edu.
authors.forename: Jeffrey K
authors.initials: JK
authors.lastname: Actor
mesh_terms: D051940:B7-2 Antigen / Q000378:metabolism; D001500:BCG Vaccine / Q000494:pharmacology*; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D058851:GPI-Linked Proteins / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D007781:Lactoferrin / Q000494:pharmacology*; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008262:Macrophage Activation / Q000187:drug effects*; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D010641:Phenotype; D017452:Receptors, IgG / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D013997:Time Factors
chemical_list: D051940:B7-2 Antigen; D001500:BCG Vaccine; C497964:CD86 protein, human; D016207:Cytokines; C428200:FCGR3B protein, human; D058851:GPI-Linked Proteins; D018836:Inflammation Mediators; C490098:LTF protein, human; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D017452:Receptors, IgG; D011994:Recombinant Proteins; C440499:lipopolysaccharide, Escherichia coli O111 B4; D007781:Lactoferrin
keywords: PBMC macrophages; Recombinant human lactoferrin; Tuberculosis