title: Priming of human neutrophils by mycobacterial lipoarabinomannans: role of granule mobilisation.
abstract: Lipoarabinomannans (LAMs) from mycobacteria were investigated concerning their effect on human neutrophils. Two types of LAM, the mannose-capped ManLAM from the virulent Mycobacterium tuberculosis H37Rv and the mannose-lacking AraLAM from a rapidly growing mycobacterial strain were used. Neither AraLAM nor ManLAM induced any significant direct activation of the NADPH-oxidase. Both LAMs, however, primed the neutrophils so that subsequent stimulation with the peptide chemoattractants fMet-Leu-Phe (fMLF), Trp-Lys-Tyr-Met-Val-DMet (WKYMVm) and the mammalian lactose-binding lectin galectin-3 resulted in a markedly enhanced oxidative response. The LAM-induced priming was accompanied by an increased exposure of complement receptors 1 and 3 as well as the formyl peptide receptor on the neutrophil surface, suggesting that the enhanced oxidative response could be due to upregulation of receptors on the cell surface as a result of granule mobilisation. Since LAM-primed neutrophils released 65% of the cell content of gelatinase but showed no increased release of vitamin B(12)-binding protein, mobilisation of the gelatinase granules rather than the specific granules is concluded to be responsible for the priming effects. This is in agreement with the subcellular localisation of receptors for fMLF, WKYMVm, as well as galectin-3, which are stored in the secretory vesicles and gelatinase granules. The priming effect appeared very similar to that of Escherichia coli lipopolysaccharide, and since no differences in activity could be detected between AraLAM and ManLAM, we hypothesize that the lipid anchor of the LAM is responsible for the priming effects.
authors.affiliation: Department of Medical Microbiology and Immunology, Göteborg University, Box 435, 405 30, Göteborg, Sweden. jenny.faldt@microbio.gu.se
authors.forename: J
authors.initials: J
authors.lastname: Fäldt
authors.forename: C
authors.initials: C
authors.lastname: Dahlgren
authors.forename: M
authors.initials: M
authors.lastname: Ridell
authors.forename: A
authors.initials: A
authors.lastname: Karlsson
mesh_terms: D003594:Cytoplasmic Granules / Q000378:metabolism*; D004306:Dose-Response Relationship, Immunologic; D018093:Gelatinases / Q000097:blood / Q000378:metabolism; D006801:Humans; D008070:Lipopolysaccharides / Q000276:immunology*; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D019255:NADPH Oxidases / Q000097:blood / Q000378:metabolism; D018375:Neutrophil Activation; D009504:Neutrophils / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology / Q000276:immunology*
chemical_list: D008070:Lipopolysaccharides; C050016:lipoarabinomannan; D019255:NADPH Oxidases; D018093:Gelatinases