Role of the Chemokine Receptors CXCR3 and CCR4 in Human Pulmonary Fibrosis

• Published in: American journal of respiratory and critical care medicine Vol. 173; no. 3; pp. 310 - 317
• Main Authors: Pignatti, Patrizia, Brunetti, Giuseppe, Moretto, Dania, Yacoub, Mona-Rita, Fiori, Marco, Balbi, Bruno, Balestrino, Antonella, Cervio, Gabriella, Nava, Stefano, Moscato, Gianna
• Format: Journal Article
• Language: English
• Published: New York, NY Am Thoracic Soc 01.02.2006; American Lung Association; American Thoracic Society
• Subjects: Adult; Aged; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Biological and medical sciences; Biopsy; Blood coagulation. Blood cells; Bronchoalveolar Lavage Fluid; Case-Control Studies; Chemokine CCL17; Chemokine CXCL10; Chemokine CXCL11; Chemokines; Chemokines, CC - metabolism; Chemokines, CXC - metabolism; Chronic obstructive pulmonary disease; Female; Fundamental and applied biological sciences. Psychology; General aspects, investigation methods, hemostasis, fibrinolysis; Humans; Intensive care medicine; Lavage; Lung diseases; Lymphocytes; Male; Medical sciences; Middle Aged; Molecular and cellular biology; Pathogenesis; Pneumology; Pneumonia; Pulmonary fibrosis; Pulmonary Fibrosis - metabolism; Pulmonary Fibrosis - pathology; Pulmonary hypertension. Acute cor pulmonale. Pulmonary embolism. Pulmonary vascular diseases; Receptors, CCR4; Receptors, Chemokine - metabolism; Receptors, CXCR3; Sarcoidosis; Sarcoidosis, Pulmonary - metabolism; Sarcoidosis, Pulmonary - pathology; Steroids; T-Lymphocytes - metabolism; Tomography; Human; Lung disease; Intensive care; Respiratory disease; Chemokine receptor; CC chemokine; chemokines; interstitial lung diseases; CXCL10; Pulmonary fibrosis; Interstitial; CXC chemokine; Resuscitation
• ISSN: 1073-449X; 1535-4970
• DOI: 10.1164/rccm.200502-244OC

The chemokine receptors CXCR3 and CCR4 have recently been described as playing a pivotal role in the mouse model of bleomycin-induced fibrosis. To evaluate the role of these receptors in human idiopathic pulmonary fibrosis (IPF). We studied 57 patients: 18 with IPF, 17 with non-IPF (nIPF), 12 with sarcoidosis, and 10 healthy control subjects. We evaluated the expression of CXCR3 and CCR4 in blood and bronchoalveolar lavage (BAL) T lymphocytes by flow cytometry and the chemokine CXCL10, CXCL11 and CCL17 BAL concentration by singular immunoassay. Patients with IPF had a significantly lower CXCR3 and a higher CCR4 expression on BAL CD4 T cells compared with the other groups. Among patients with IPF, those treated with corticosteroids exhibited higher CXCR3 and lower CCR4 expression compared with untreated patients. CXCR3 expression correlated with BAL lymphocytes and CCR4 with BAL neutrophils and eosinophils. CXCL10 levels correlated with the expression of CXCR3 on BAL CD4 cells. CXCL11 was undetectable in almost all patients, whereas CCL17 was primarily detectable in patients with IPF. The percentage of BAL CCR4CD4 cells negatively correlated with DL(CO). The changes in the total lung capacity, VC, and of the alveolar-arterial PO2 gradient in patients with IPF and those with nIPF 6 to 12 mo after the first evaluation were associated with CD4CXCR3 percentage on BAL cells. We found an imbalance in CXCR3/CCR4 expression on BAL CD4 lymphocytes and reduced CXCL10 BAL levels in patients with IPF, suggesting a pivotal role of these molecules in IPF.