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Enhanced Monocyte Chemoattractant Protein-3/CC Chemokine Ligand-7 in Usual Interstitial Pneumonia

Department of Pathology, Department of Medicine, Division of Pulmonary and Critical Care Medicine, and Department of Radiology, University of Michigan Medical School, Ann Arbor, Michigan; Mayo Clinic, Scottsdale, Arizona; and Armed Forces Institute of Pathology, Washington, DC

Correspondence and requests for reprints should be addressed to Cory M. Hogaboam, Ph.D., Associate Professor, Department of Pathology, University of Michigan Medical School, Rm. 5216B, Med Sci I, 1301 Catherine Rd., Ann Arbor, MI 48109-0602. 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), nonspecific interstitial pneumonia, and respiratory bronchiolitis-interstitial lung disease, but not patients without IIP, 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 patients with nonspecific interstitial pneumonia, respiratory bronchiolitis-interstitial lung disease, and from patients without IIP. 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 patients with UIP relative to patients with other IIP and patients without IIP, and that this CC chemokine may have a major role in the progression of fibrosis in this IIP patient group.

Key Words: chemokine • chemokine receptor • idiopathic interstitial pneumonia • idiopathic pulmonary fibrosis

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