title: Mycobacterium tuberculosis 19-kDa lipoprotein promotes neutrophil activation.
abstract: Certain microbial substances, e.g., LPS, can activate neutrophils or prime them to enhance their response to other activating agents, e.g., fMLP. We investigated the role of the Mycobacterium tuberculosis (MTB) 19-kDa lipoprotein in activation of human neutrophils. MTB 19-kDa lipoprotein initiated phenotypic changes characteristic of neutrophil activation, including down-regulation of CD62 ligand (L-selectin) and up-regulation of CD35 (CR1) and CD11b/CD18 (CR3, Mac-1). In addition, exposure of neutrophils to MTB 19-kDa lipoprotein enhanced the subsequent oxidative burst in response to fMLP as assessed by oxidation of dihydrorhodamine 123 (determined by flow cytometry). LPS also produced these effects with similar kinetics, but an oligodeoxynucleotide containing a CpG motif failed to induce any priming or activation response. Although the effects of LPS required the presence of serum, neutrophil activation by MTB 19-kDa lipoprotein occurred independently of serum factors, suggesting the involvement of different receptors and signaling mechanisms for LPS and MTB 19-kDa lipoprotein. Thus, MTB 19-kDa lipoprotein serves as a pathogen-associated molecular pattern that promotes neutrophil priming and activation.
authors.affiliation: Department of Pathology, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, USA.
authors.forename: C
authors.initials: C
authors.lastname: Neufert
authors.forename: R K
authors.initials: RK
authors.lastname: Pai
authors.forename: E H
authors.initials: EH
authors.lastname: Noss
authors.forename: M
authors.initials: M
authors.lastname: Berger
authors.forename: W H
authors.initials: WH
authors.lastname: Boom
authors.forename: C V
authors.initials: CV
authors.lastname: Harding
mesh_terms: D001426:Bacterial Proteins / Q000494:pharmacology*; D018821:CD18 Antigens / Q000096:biosynthesis; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D016895:Culture Media, Serum-Free; D004306:Dose-Response Relationship, Immunologic; D015536:Down-Regulation / Q000276:immunology; D006801:Humans; D019041:L-Selectin / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology; D008074:Lipoproteins / Q000494:pharmacology*; D016177:Macrophage-1 Antigen / Q000096:biosynthesis; D009169:Mycobacterium tuberculosis / Q000276:immunology* / Q000472:pathogenicity; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D018375:Neutrophil Activation / Q000276:immunology*; D009504:Neutrophils / Q000378:metabolism; D017463:Receptors, Complement 3b / Q000096:biosynthesis; D016897:Respiratory Burst / Q000276:immunology; D015854:Up-Regulation / Q000276:immunology
chemical_list: C087864:19 kDa antigen, Mycobacterium; D001426:Bacterial Proteins; D018821:CD18 Antigens; D016895:Culture Media, Serum-Free; D008070:Lipopolysaccharides; D008074:Lipoproteins; D016177:Macrophage-1 Antigen; D017463:Receptors, Complement 3b; D019041:L-Selectin; D009240:N-Formylmethionine Leucyl-Phenylalanine