RT Journal Article
SR Electronic
T1 The Presence of a Matrix-Derived Neutrophil Chemoattractant in Bronchiolitis Obliterans Syndrome after Lung Transplantation
JF The Journal of Immunology
JO J. Immunol.
FD American Association of Immunologists
SP 4423
OP 4431
DO 10.4049/jimmunol.0802457
VO 182
IS 7
A1 Hardison, Matthew T.
A1 Galin, F. Shawn
A1 Calderon, Christopher E.
A1 Djekic, Uros V.
A1 Parker, Suzanne B.
A1 Wille, Keith M.
A1 Jackson, Patricia L.
A1 Oster, Robert A.
A1 Young, K. Randall
A1 Blalock, J. Edwin
A1 Gaggar, Amit
YR 2009
UL http://www.jimmunol.org/content/182/7/4423.abstract
AB Lung transplantation is a therapeutic modality frequently used in end-stage lung disease. Unfortunately, lung transplant recipients have poor clinical outcomes, often due to the development of bronchiolitis obliterans syndrome (BOS). This process is often characterized by the pathologic findings of obliterative bronchiolitis: neutrophil influx and extracellular matrix remodeling leading to luminal obstruction and airway inflammation. The molecular mechanisms underlying BOS are poorly understood and disease-specific biomarkers are lacking. We report that in addition to increased levels of IL-8, the level of the neutrophil chemoattractant proline-glycine-proline (PGP) is elevated in BOS patient bronchoalveolar lavage (BAL) fluid. The enzymes responsible for generating PGP, matrix metalloproteases 8 and -9 and prolyl endopeptidase, are also elevated in these samples. Together, IL-8 and PGP account for most of the neutrophil chemoattractant capacity seen in BOS BAL fluid. Using specific neutralizing Abs to both IL-8 and PGP, we demonstrate that PGP is a prominent neutrophil chemoattractant found in BAL fluid from individuals at the time of diagnosis of BOS. These findings highlight the influence of a matrix-derived neutrophil chemoattractant in posttransplantation BOS and provide opportunities for the development of unique diagnostics and therapeutics to potentially improve disease outcomes.