title: Endogenous MCP-1 promotes lung inflammation induced by LPS and LTA.
abstract: Monocyte chemoattractant protein 1 (MCP-1) plays an important role in leukocyte recruitment to sites of infection and inflammation. In addition, MCP-1 may attenuate inflammation by virtue of its capacity to inhibit the production of proinflammatory cytokines. We here investigated the role of MCP-1 in lung inflammation induced by lipopolysaccharide (LPS) or lipoteichoic acid (LTA), constituents of the gram-negative and gram-positive bacterial cell wall, respectively. Healthy humans demonstrated elevated MCP-1 concentrations in their bronchoalveolar lavage fluid (BALF) 6h after inhalation of LPS. Similarly, intranasal administration of LPS or LTA to mice resulted in a rise in BALF MCP-1 levels. Murine alveolar macrophage-like cells released significant amounts of MCP-1 upon stimulation with LPS or LTA in vitro. Compared to Wt mice, MCP-1(-/-) mice demonstrated lower TNF-α levels and a diminished neutrophil influx into their bronchoalveolar space after either LPS or LTA instillation. After intrapulmonary delivery of LPS MCP-1(-/-) mice had decreased interleukin-6 and KC concentrations and less severe lung inflammation upon histopathological examination. Remarkably, MCP-1 deficiency was associated with an early enhancement of interleukin-10 release in BALF after both LPS and LTA instillation. These data suggest that MCP-1 is a proinflammatory mediator during pulmonary inflammation induced by either LPS or LTA.
authors.affiliation: Center for Infection and Immunity Amsterdam, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. M.A.vanZoelen@amc.uva.nl
authors.forename: Marieke A D
authors.initials: MA
authors.lastname: van Zoelen
authors.forename: Marleen I
authors.initials: MI
authors.lastname: Verstege
authors.forename: Christian
authors.initials: C
authors.lastname: Draing
authors.forename: Regina
authors.initials: R
authors.lastname: de Beer
authors.forename: Cornelis
authors.initials: C
authors.lastname: van't Veer
authors.forename: Sandrine
authors.initials: S
authors.lastname: Florquin
authors.forename: Paul
authors.initials: P
authors.lastname: Bresser
authors.forename: Jaring S
authors.initials: JS
authors.lastname: van der Zee
authors.forename: Anje A
authors.initials: AA
authors.lastname: te Velde
authors.forename: Sonja
authors.initials: S
authors.lastname: von Aulock
authors.forename: Tom
authors.initials: T
authors.lastname: van der Poll
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002452:Cell Count; D018932:Chemokine CCL2 / Q000172:deficiency / Q000502:physiology*; D002634:Chemotaxis, Leukocyte; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008070:Lipopolysaccharides / Q000276:immunology*; D008168:Lung / Q000276:immunology*; D016676:Macrophages, Alveolar / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009504:Neutrophils / Q000276:immunology; D011014:Pneumonia / Q000276:immunology*; D013682:Teichoic Acids / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D055815:Young Adult
chemical_list: D018932:Chemokine CCL2; D016207:Cytokines; D015850:Interleukin-6; D008070:Lipopolysaccharides; D013682:Teichoic Acids; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; C009900:lipoteichoic acid