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Role of the chemokine receptors CXCR3 and CCR4 in human pulmonary fibrosis.
Am J Respir Crit Care Med. 2006 Feb 01; 173(3):310-7.AJ

Abstract

RATIONALE

The chemokine receptors CXCR3 and CCR4 have recently been described as playing a pivotal role in the mouse model of bleomycin-induced fibrosis.

OBJECTIVES

To evaluate the role of these receptors in human idiopathic pulmonary fibrosis (IPF).

METHODS

We studied 57 patients: 18 with IPF, 17 with non-IPF (nIPF), 12 with sarcoidosis, and 10 healthy control subjects.

MEASUREMENTS

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.

MAIN RESULTS

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.

CONCLUSIONS

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.

Authors+Show Affiliations

Allergy and Immunology Unit, Rehabilitative Pneumology Department, Pavia, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

16239626

Citation

Pignatti, Patrizia, et al. "Role of the Chemokine Receptors CXCR3 and CCR4 in Human Pulmonary Fibrosis." American Journal of Respiratory and Critical Care Medicine, vol. 173, no. 3, 2006, pp. 310-7.
Pignatti P, Brunetti G, Moretto D, et al. Role of the chemokine receptors CXCR3 and CCR4 in human pulmonary fibrosis. Am J Respir Crit Care Med. 2006;173(3):310-7.
Pignatti, P., Brunetti, G., Moretto, D., Yacoub, M. R., Fiori, M., Balbi, B., Balestrino, A., Cervio, G., Nava, S., & Moscato, G. (2006). Role of the chemokine receptors CXCR3 and CCR4 in human pulmonary fibrosis. American Journal of Respiratory and Critical Care Medicine, 173(3), 310-7.
Pignatti P, et al. Role of the Chemokine Receptors CXCR3 and CCR4 in Human Pulmonary Fibrosis. Am J Respir Crit Care Med. 2006 Feb 1;173(3):310-7. PubMed PMID: 16239626.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Role of the chemokine receptors CXCR3 and CCR4 in human pulmonary fibrosis. AU - Pignatti,Patrizia, AU - Brunetti,Giuseppe, AU - Moretto,Dania, AU - Yacoub,Mona-Rita, AU - Fiori,Marco, AU - Balbi,Bruno, AU - Balestrino,Antonella, AU - Cervio,Gabriella, AU - Nava,Stefano, AU - Moscato,Gianna, Y1 - 2005/10/20/ PY - 2005/10/22/pubmed PY - 2006/4/8/medline PY - 2005/10/22/entrez SP - 310 EP - 7 JF - American journal of respiratory and critical care medicine JO - Am J Respir Crit Care Med VL - 173 IS - 3 N2 - RATIONALE: The chemokine receptors CXCR3 and CCR4 have recently been described as playing a pivotal role in the mouse model of bleomycin-induced fibrosis. OBJECTIVES: To evaluate the role of these receptors in human idiopathic pulmonary fibrosis (IPF). METHODS: We studied 57 patients: 18 with IPF, 17 with non-IPF (nIPF), 12 with sarcoidosis, and 10 healthy control subjects. MEASUREMENTS: 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. MAIN RESULTS: 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. CONCLUSIONS: 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. SN - 1073-449X UR - https://www.unboundmedicine.com/medline/citation/16239626/Role_of_the_chemokine_receptors_CXCR3_and_CCR4_in_human_pulmonary_fibrosis_ L2 - https://www.atsjournals.org/doi/10.1164/rccm.200502-244OC?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -