title: Lipocalin-2 ameliorates granulocyte functionality.
abstract: Attraction of neutrophils to sites of infection or tissue injury is an essential prerequisite for an efficient innate immune response. Herein, we provide novel evidence that the antimicrobial protein, neutrophil gelatinase associated lipocalin (24p3 or lipocalin-2, Lcn2) is a central regulator of this process. Lcn2 is produced by several cell types but high amounts are released by neutrophils. Using human and murine neutrophils, we found that the addition of recombinant Lcn2 significantly stimulated their migration, which was independent of IL-8/keratinocyte chemokine formation. Mechanistically, this could be traced back to Lcn2-mediated changes of Erk1/2 signaling. Accordingly, the i.p. injection of Lcn2 into C57BL/6 mice stimulated the mobilization of neutrophils while we found a significantly reduced neutrophil chemotactic activity of cells obtained from Lcn2 KO mice. This observation transmitted to a reduced accumulation of neutrophils in intra-dermal lesions infected with Salmonella typhimurium in Lcn2 KO mice as compared to WT mice. This was not only due to a reduced chemotaxis but also to an impaired cellular adhesion of neutrophils in the absence of Lcn2. We herein describe a novel role of Lcn2 as an important paracrine chemoattractant and an indispensable factor for neutrophil function in inflammation.
authors.affiliation: Department of Internal Medicine, Clinical Immunology and Infectious Diseases, Medical University Innsbruck, Innsbruck, Austria.
authors.forename: Andrea
authors.initials: A
authors.lastname: Schroll
authors.forename: Kathrin
authors.initials: K
authors.lastname: Eller
authors.forename: Clemens
authors.initials: C
authors.lastname: Feistritzer
authors.forename: Manfred
authors.initials: M
authors.lastname: Nairz
authors.forename: Thomas
authors.initials: T
authors.lastname: Sonnweber
authors.forename: Patrizia A
authors.initials: PA
authors.lastname: Moser
authors.forename: Alexander R
authors.initials: AR
authors.lastname: Rosenkranz
authors.forename: Igor
authors.initials: I
authors.lastname: Theurl
authors.forename: Guenter
authors.initials: G
authors.lastname: Weiss
mesh_terms: D000209:Acute-Phase Proteins / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D000818:Animals; D002633:Chemotaxis / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000276:immunology; D000071068:Lipocalin-2; D054834:Lipocalins / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009504:Neutrophils / Q000276:immunology*; D015513:Oncogene Proteins / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D019899:Paracrine Communication / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D012480:Salmonella Infections / Q000235:genetics / Q000276:immunology; D012486:Salmonella typhimurium / Q000276:immunology
chemical_list: D000209:Acute-Phase Proteins; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; C071332:Lcn2 protein, mouse