TY - JOUR
T1 - A novel peptide CXCR ligand derived from extracellular matrix degradation during airway inflammation
AU - Weathington, N.M.
AU - Van Houwelingen, A.H.
AU - Noerager, B.D.
AU - Jackson, P.L.
AU - Kraneveld, A.D.
AU - Galin, F.S.
AU - Folkerts, G.
AU - Nijkamp, F.P.
AU - Blalock, J.E.
PY - 2006/3
Y1 - 2006/3
N2 - We describe the tripeptide neutrophil chemoattractant N-acetyl Pro-Gly-Pro (PGP), derived from the breakdown of extracellular matrix (ECM), which shares sequence and structural homology with an important domain on alpha chemokines. PGP caused chemotaxis and production of superoxide through CXC receptors, and administration of peptide caused recruitment of neutrophils (PMNs) into lungs of control, but not CXCR2-deficient mice. PGP was generated in mouse lung after exposure to lipopolysaccharide, and in vivo and in vitro blockade of PGP with monoclonal antibody suppressed PMN responses as much as chemokine-specific monoclonal antibody. Extended PGP treatment caused alveolar enlargement and right ventricular hypertrophy in mice. PGP was detectable in substantial concentrations in a majority of bronchoalveolar lavage samples from individuals with chronic obstructive pulmonary disease, but not control individuals. Thus, PGP's activity links degradation of ECM with neutrophil recruitment in airway inflammation, and PGP may be a biomarker and therapeutic target for neutrophilic inflammatory diseases. © 2006 Nature Publishing Group.
AB - We describe the tripeptide neutrophil chemoattractant N-acetyl Pro-Gly-Pro (PGP), derived from the breakdown of extracellular matrix (ECM), which shares sequence and structural homology with an important domain on alpha chemokines. PGP caused chemotaxis and production of superoxide through CXC receptors, and administration of peptide caused recruitment of neutrophils (PMNs) into lungs of control, but not CXCR2-deficient mice. PGP was generated in mouse lung after exposure to lipopolysaccharide, and in vivo and in vitro blockade of PGP with monoclonal antibody suppressed PMN responses as much as chemokine-specific monoclonal antibody. Extended PGP treatment caused alveolar enlargement and right ventricular hypertrophy in mice. PGP was detectable in substantial concentrations in a majority of bronchoalveolar lavage samples from individuals with chronic obstructive pulmonary disease, but not control individuals. Thus, PGP's activity links degradation of ECM with neutrophil recruitment in airway inflammation, and PGP may be a biomarker and therapeutic target for neutrophilic inflammatory diseases. © 2006 Nature Publishing Group.
UR - http://www.scopus.com/inward/record.url?scp=33644828187&partnerID=8YFLogxK
U2 - 10.1038/nm1361
DO - 10.1038/nm1361
M3 - Article
SN - 1078-8956
VL - 12
SP - 317
EP - 323
JO - Nature Medicine
JF - Nature Medicine
IS - 3
ER -