title: Trappin-2 promotes early clearance of Pseudomonas aeruginosa through CD14-dependent macrophage activation and neutrophil recruitment.
abstract: Microaspiration of Pseudomonas aeruginosa contributes to the pathogenesis of nosocomial pneumonia. Trappin-2 is a host defense peptide that assists with the clearance of P. aeruginosa through undefined mechanisms. A model of macrophage interactions with replicating P. aeruginosa (strain PA01) in serum-free conditions was developed, and the influence of subantimicrobial concentrations of trappin-2 was subsequently studied. PA01 that was pre-incubated with trappin-2 (at concentrations that have no direct antimicrobial effects), but not control PA01, was cleared by alveolar and bone marrow-derived macrophages. However, trappin-2-enhanced clearance of PA01 was completely abrogated by CD14- null macrophages. Fluorescence microscopy demonstrated the presence of trappin-2 on the bacterial cell surface of trappin-2-treated PA01. In a murine model of early lung infection, trappin-2-treated PA01 was cleared more efficiently than control PA01 2 hours of intratracheal instillation. Furthermore, trappin-2-treated PA01 up-regulated the murine chemokine CXCL1/KC after 2 hours with a corresponding increase in neutrophil recruitment 1 hour later. These in vivo trappin-2-treated PA01 effects were absent in CD14-deficient mice. Trappin-2 appears to opsonize P. aeruginosa for more efficient, CD14-dependent clearance by macrophages and contributes to the induction of chemokines that promote neutrophil recruitment. Trappin-2 may therefore play an important role in innate recognition and clearance of pathogens during the very earliest stages of pulmonary infection.
authors.affiliation: MRC Centre for Inflammation Research, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK.
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Wilkinson
authors.forename: Kevin
authors.initials: K
authors.lastname: Dhaliwal
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Hamilton
authors.forename: Alexander F
authors.initials: AF
authors.lastname: Lipka
authors.forename: Lesley
authors.initials: L
authors.lastname: Farrell
authors.forename: Donald J
authors.initials: DJ
authors.lastname: Davidson
authors.forename: Rodger
authors.initials: R
authors.lastname: Duffin
authors.forename: Andrew Conway
authors.initials: AC
authors.lastname: Morris
authors.forename: Chris
authors.initials: C
authors.lastname: Haslett
authors.forename: John R W
authors.initials: JR
authors.lastname: Govan
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Gregory
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Sallenave
authors.forename: A John
authors.initials: AJ
authors.lastname: Simpson
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D018920:Coculture Techniques; D053492:Elafin / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D007150:Immunohistochemistry; D018950:Lipopolysaccharide Receptors / Q000276:immunology*; D008171:Lung Diseases / Q000276:immunology / Q000382:microbiology; D008262:Macrophage Activation / Q000276:immunology*; D008264:Macrophages / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D020556:Neutrophil Infiltration / Q000276:immunology*; D010587:Phagocytosis; D011552:Pseudomonas Infections / Q000276:immunology*; D011550:Pseudomonas aeruginosa / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology
chemical_list: D053492:Elafin; D018950:Lipopolysaccharide Receptors; D011994:Recombinant Proteins