title: Myeloid-related protein-14 deficiency promotes inflammation in staphylococcal pneumonia.
abstract: Staphylococcus aureus has evolved as an important cause of pneumonia in both hospital and community settings. Staphylococcal lung infection can lead to overwhelming pulmonary inflammation. During infection, neutrophils release complexes of myeloid-related protein (MRP)8 and MRP14 (MRP8/14). MRP8/14 has been shown to exert pro-inflammatory and chemotactic activity, and to assist in the killing of S. aureus. In the current study we sought to determine the role of MRP8/14 in the host response during S. aureus pneumonia.Pneumonia was induced in wildtype and MRP14-deficient mice (mice unable to form MRP8/14) by intranasal inoculation of 1×10(7) CFU of S. aureus USA300. Mice were sacrificed at 6, 24, 48 or 72 h after infection for analyses.S. aureus pneumonia was associated with a strong rise in MRP8/14 in bronchoalveolar lavage fluid and lung tissue. Surprisingly, MRP14 deficiency had a limited effect on bacterial clearance and was associated with increased cytokine levels in bronchoalveolar lavage fluid and aggravated lung histopathology. MRP14 deficiency in addition was associated with a diminished transmigration of neutrophils into bronchoalveolar lavage fluid at late time-points after infection together with reduced release of nucleosomes.MRP8/14 serves in an unexpected protective role for the lung in staphylococcal pneumonia.
authors: Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands Center for Infection and Immunity Amsterdam, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands a.achouiti@amc.nl.
authors: Ahmed
authors: A
authors: Achouiti
authors: Institute of Immunology, University of Munster, Munster, Germany.
authors: Thomas
authors: T
authors: Vogl
authors: Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands Center for Infection and Immunity Amsterdam, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors: Anne J
authors: AJ
authors: Van der Meer
authors: Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands Center for Infection and Immunity Amsterdam, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors: Ingrid
authors: I
authors: Stroo
authors: Dept of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors: Sandrine
authors: S
authors: Florquin
authors: Dept of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors: Onno J
authors: OJ
authors: de Boer
authors: Institute of Immunology, University of Munster, Munster, Germany.
authors: Johannes
authors: J
authors: Roth
authors: Dept of Hematology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands Dept of Immunopathology, Sanquin Research, Amsterdam, The Netherlands.
authors: Sacha
authors: S
authors: Zeerleder
authors: Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands Center for Infection and Immunity Amsterdam, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors: Cornelis
authors: C
authors: van 't Veer
authors: Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands Center for Infection and Immunity Amsterdam, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors: Alex F
authors: AF
authors: de Vos
authors: Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands Center for Infection and Immunity Amsterdam, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands Division of Infectious Diseases, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors: Tom
authors: T
authors: van der Poll
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D040501:Calgranulin A / Q000378:metabolism; D040502:Calgranulin B / Q000235:genetics / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D007249:Inflammation / Q000382:microbiology*; D008168:Lung / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000378:metabolism*; D011023:Pneumonia, Staphylococcal / Q000473:pathology*; D013211:Staphylococcus aureus
chemical_list: D040501:Calgranulin A; D040502:Calgranulin B; D016207:Cytokines