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Am J Respir Crit Care Med. 2006 Apr 1;173(7):781-92. Epub 2006 Jan 13.

A vicious circle of alveolar macrophages and fibroblasts perpetuates pulmonary fibrosis via CCL18.

Author information

  • 1Department of Pneumology, University Hospital, Killianstr. 5, 79106 Freiburg, Germany. prasse@medizin.ukl.uni-freiburg.de

Abstract

RATIONALE:

Recently, models of macrophage activation have been revised. Macrophages stimulated with Th2 cytokines have been classified as alternatively activated.

OBJECTIVES:

This article examines the expression and regulation of CC chemokine ligand 18 (CCL18), a marker of alternative activation, by human alveolar macrophages (AMs).

METHODS:

AM were obtained from bronchoalveolar lavage (BAL) fluid of patients with idiopathic pulmonary fibrosis, sarcoidosis, or hypersensitivity pneumonitis (n = 69) and healthy volunteers (n = 22). Expression of CCL18 was determined by quantitative reverse transcriptase-polymerase chain reaction, in situ hybridization, flow cytometry, and immunohistochemistry, respectively.

MEASUREMENTS AND MAIN RESULTS:

Spontaneous CCL18 production by BAL-derived cells was markedly increased in patients with pulmonary fibrosis and correlated negatively with pulmonary function test parameters. CCL18 gene expression and protein production were up-regulated in normal AMs after Th2 cytokine stimulation and/or coculture with human lung fibroblasts. Native collagen significantly up-regulated CCL18 expression in normal AMs activated with Th2 cytokines via a mechanism mediated by beta2-integrin/ scavenger receptor(s). Culture supernatants of AMs from patients with idiopathic pulmonary fibrosis increased collagen production by normal lung fibroblasts partly mediated via CCL18.

CONCLUSIONS:

Our findings suggest that AMs from patients with pulmonary fibrosis disclose a phenotype of alternative activation and might be a part of a positive feedback loop with lung fibroblasts perpetuating fibrotic processes.

PMID:
16415274
[PubMed - indexed for MEDLINE]
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