Published ahead of print on June 10, 2004, doi:10.1164/rccm.200401-002OC
Am. J. Respir. Crit. Care Med., Volume 170, Number 5, September 2004, 508-515
A more recent version of this article appeared on September 1, 2004
Submitted on January 8, 2004
Accepted on June 7, 2004
Enhanced Monocyte Chemoattractant Protein-3/CC Chemokine Ligand-7 in Usual Interstitial Pneumonia
Esther S Choi1, Claudia Jakubzick1, Kristin J Carpenter1, Steven L Kunkel1, Holly Evanoff1, Fernando J Martinez2, Kevin R Flaherty2, Galen B Toews2, Thomas V Colby3, Ella A Kazerooni4, Barry H Gross4, William D Travis5, and Cory M Hogaboam1*
1 Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA,
2 Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of Michigan Medical School, Ann Arbor, MI, USA,
3 Mayo Clinic, Scottsdale, AZ, USA,
4 Department of Radiology, University of Michigan Medical School, Ann Arbor, MI, USA,
5 Armed Forces Institute of Pathology, Washington, DC, USA
* To whom correspondence should be addressed. E-mail: hogaboam{at}med.umich.edu.
Chemokines are increased and may exert effects on both inflammatory and remodeling events in idiopathic pulmonary pneumonia (IIP). Accordingly, we examined the concomitant expression of inflammatory CC chemotactic cytokines or chemokines and their corresponding receptors in surgical lung biopsies obtained at the time of disease diagnosis and pulmonary fibroblasts grown from these biopsies. By gene array analysis, upper and lower lobe biopsies and primary fibroblast lines from patients with usual interstitial pneumonia (UIP), non-specific interstitial pneumonia (NSIP), and respiratory bronchiolitis-interstitial lung disease (RBILD), but not non-IIP patients, exhibited CCL7 gene expression. TAQMAN, immunohistochemical, and ELISA analyses confirmed that CCL7 was expressed at significantly higher levels in UIP lung biopsies compared with biopsies from NSIP, RBILD, and non-IIP patients. Higher levels of CCL7 were present in cultures of IIP fibroblasts compared with non-IIP fibroblasts, and CCL5, a CCR5 agonist, significantly increased the synthesis of CCL7 by UIP fibroblasts. Together, these data suggest that CCL7 is highly expressed in biopsies and pulmonary fibroblast lines obtained from UIP patients relative to other IIP and non-IIP patients, and this CC chemokine may have a major role in the progression of fibrosis in this IIP patient group.
Key words: Idiopathic interstitial pneumonia, Idiopathic pulmonary fibrosis, Chemokine, Chemokine Receptor
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