ORIGINAL ARTICLE

Focal interstitial CC chemokine receptor 7 (CCR7) expression in idiopathic interstitial pneumonia

E S Choi¹, E M Pierce¹, C Jakubzick¹, K J Carpenter¹, S L Kunkel¹, H Evanoff¹, F J Martinez², K R Flaherty², B B Moore², G B Toews², T V Colby³, E A Kazerooni⁴, B H Gross⁴, W D Travis⁵, C M Hogaboam¹

¹ Department of Pathology, University of Michigan Medical School, Room 5214, Medical Science I, 1301 Catherine Road, Ann Arbor, MI 48109-0602, USA
² Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Michigan Medical School
³ Mayo Clinic, Scottsdale, Arizona, USA
⁴ Department of Radiology University of Michigan Medical School
⁵ Armed Forces Institute of Pathology, Washington, DC 20306-6000, USA

Correspondence to:
Correspondence to:
Dr C M Hogaboam
Department of Pathology, University of Michigan Medical School, Room 5214, Medical Science I, 1301 Catherine Road, Ann Arbor, MI 48109-0602, USA; Hogaboam{at}med.umich.edu

Background/Aims: Idiopathic interstitial pneumonias (IIPs) are a diverse grouping of chronic pulmonary diseases characterised by varying degrees of pulmonary fibrosis. The triggers of the fibroproliferative process in IIP remain enigmatic but recent attention has been directed towards chemokine involvement in this process.

Methods: The expression of two chemokine receptors, CCR7 and CXCR4, and their respective ligands, CCL19, CCL21, and CXCL12, were examined in surgical lung biopsies (SLBs) from patients with IIP. Transcript and protein expression of these receptors and their ligands was compared with that detected in histologically normal margin SLBs.

Results: CCR7 and CXCR4 were detected by gene array and real time polymerase chain reaction analysis and CCR7, but not CXCR4, expression was significantly raised in usual interstitial pneumonia (UIP) relative to biopsies from patients diagnosed with non-specific interstitial pneumonia (NSIP) or respiratory bronchiolitis/interstitial lung disease (RBILD). CCR7 protein was expressed in interstitial areas of all upper and lower lobe UIP SLBs analysed. CCR7 expression was present in 50% of NSIP SLBs, and CCR7 was restricted to blood vessels and mononuclear cells in 75% of RBILD SLBs. Immune cell specific CXCR4 expression was seen in IIP and normal margin biopsies. CCR7 positive areas in UIP biopsies were concomitantly positive for CD45 (the leucocyte common antigen) but CCR7 positive areas in all IIP SLBs lacked the haemopoietic stem cell antigen CD34, collagen 1, and  smooth muscle actin.

Conclusion: This molecular and immunohistochemical analysis showed that IIPs are associated with abnormal CCR7 transcript and protein expression.

Abbreviations: CCR/L, CC chemokine receptor/ligand; CXCR/L, CX chemokine receptor/ligand; ELISA, enzyme linked immunosorbent assay; GAPDH, glyceraldehyde 3-phosphate dehydrogenase; IIP, idiopathic interstitial pneumonia; NSIP, non-specific interstitial pneumonia; PCR, polymerase chain reaction; RBILD, respiratory bronchiolitis/interstitial lung disease; SLB, surgical lung biopsy; SMA, smooth muscle actin; UIP, usual interstitial pneumonia

Keywords: chemokine; chemokine receptor; idiopathic interstitial pneumonia; fibrocyte

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