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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.

Original publication

DOI

10.2353/ajpath.2009.080746

Type

Journal article

Journal

Am j pathol

Publication Date

04/2009

Volume

174

Pages

1338 - 1346

Keywords

Animals, Cells, Cultured, Coculture Techniques, Elafin, Female, Flow Cytometry, Immunohistochemistry, Lipopolysaccharide Receptors, Lung Diseases, Macrophage Activation, Macrophages, Mice, Mice, Inbred C57BL, Microscopy, Fluorescence, Neutrophil Infiltration, Phagocytosis, Pseudomonas Infections, Pseudomonas aeruginosa, Recombinant Proteins