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The Proceedings of the American Thoracic Society 5:375 (2008)
© 2008 The American Thoracic Society
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Neutrophil Chemotactic Collagen Fragments Are Generated from Cystic Fibrosis Sputum

Patricia L. Jackson1, J. Edwin Blalock1 and Amit Gaggar1,2

Departments of 1 Physiology/Biophysics and 2 Medicine, University of Alabama-Birmingham, Birmingham, Alabama

Correspondence and requests for reprints should be addressed to Amit Gaggar, M.D., Ph.D., Assistant Professor, Department of Medicine, University of Alabama-Birmingham, 424 THT, 1900 University Blvd., Birmingham, AL 35294. E-mail: agaggar{at}uab.edu

Lung remodeling is a feature of many chronic lung diseases, leading to structural changes in airways and parenchyma. An interesting feature of this remodeling is the role it may play in ongoing airway inflammation. Attention has focused on matrix-derived cleavage products as chemoattractants in chronic neutrophilic lung diseases such as cystic fibrosis (CF). Our lab has characterized a collagen fragment, proline-glycine-proline (PGP), which serves as a neutrophil chemoattractant in a murine model of LPS-induced lung injury and is present in CF specimens. We hypothesized that sputum from patients with CF had the capability of generating PGP from intact collagen and that elevated matrix metalloprotease (MMP) activity in CF sputum contributed to PGP generation.

CF sputum was collected from inpatients with CF with active exacerbation (n = 10) and control subjects without CF (n = 5). CF sputum was incubated with intact collagen, with and without MMP inhibitors. These samples were then examined for PGP generation via tandem mass spectrometry. CF sputum, when placed on intact collagen, is capable of generating PGP in quantities 10-fold greater than levels generated from the sputum of normal control subjects (P < 0.05). PGP production from CF sputum was inhibited 80% with pre-incubation with an MMP-9–specific inhibitor (P < 0.01).

PGP is an important chemoattractant seen in CF. The enzymatic components necessary for the generation of PGP are elevated in CF sputum compared with sputum from normal control subjects. The use of an MMP-9 inhibitor demonstrated a significant decrease in PGP production from CF sputum and points to a central role of MMP-9 in PGP generation

FOOTNOTES

Supported by NIH RO1 HL090999 and HL077783 (to J.E.B.), and CFF GAGGAR07A0 (to A.G.).

Conflict of Interest Statement: None of the authors has a financial relationship with a commercial entity that has an interest in the subject of this manuscript.

(Received in original form November 11, 2007; accepted in final form November 16, 2007)





This Article
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Right arrow Articles by Jackson, P. L.
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Right arrow Articles by Jackson, P. L.
Right arrow Articles by Gaggar, A.

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