Alternatively activated alveolar macrophages in pulmonary fibrosis-mediator production and intracellular signal transduction

Dmitri V Pechkovsky; Antje Prasse; Florian Kollert; Kathrin M Y Engel; Jan Dentler; Werner Luttmann; Karlheinz Friedrich; Joachim Müller-Quernheim; Gernot Zissel

doi:10.1016/j.clim.2010.06.017

Alternatively activated alveolar macrophages in pulmonary fibrosis-mediator production and intracellular signal transduction

Clin Immunol. 2010 Oct;137(1):89-101. doi: 10.1016/j.clim.2010.06.017. Epub 2010 Jul 31.

Authors

Dmitri V Pechkovsky¹, Antje Prasse, Florian Kollert, Kathrin M Y Engel, Jan Dentler, Werner Luttmann, Karlheinz Friedrich, Joachim Müller-Quernheim, Gernot Zissel

Affiliation

¹ Department of Pneumology, Medical Center, Albert-Ludwigs University, Freiburg, Germany.

PMID: 20674506
DOI: 10.1016/j.clim.2010.06.017

Abstract

Activated macrophages have been characterized as M1 and M2 according to their inflammatory response pattern. Here we analyzed the M2 marker expression and intracellular signal transduction in the course of cytokine-driven differentiation. We found elevated spontaneous production of the chemokines CCL17, CCL18 and CCL22 and increased expression of CD206 by alveolar macrophages from patients with lung fibrosis. Stimulation of normal human AM with Th2 cytokines IL-4 and/or IL-10 in vitro revealed IL-4 as the most powerful inducer of M2-phenotype in AM and monocytes. Importantly, IL-10 enhanced IL-4-induced expression of CCL18 and IL-1RA in a synergistic fashion. IL-4/IL-10 stimulation induces a strong activation of STAT3 in AM from fibrosis patients. These results suggest an important role for M2 polarized AM in the pathogenesis of pulmonary fibrosis and indicate that both IL-4 and IL-10 account for human AM phenotype shift to M2, as seen in patients with fibrotic interstitial lung diseases.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Aged, 80 and over
Bronchoalveolar Lavage Fluid / cytology
Chemokines, CC / genetics
Chemokines, CC / metabolism
Cytokines / metabolism*
Female
Gene Expression / drug effects
Humans
Idiopathic Pulmonary Fibrosis / immunology
Idiopathic Pulmonary Fibrosis / metabolism
Interleukin 1 Receptor Antagonist Protein / genetics
Interleukin 1 Receptor Antagonist Protein / metabolism
Interleukin-10 / pharmacology
Interleukin-4 / pharmacology
Interleukin-8 / metabolism
Lectins, C-Type / metabolism
Macrophage Activation / drug effects
Macrophage Activation / immunology*
Macrophages, Alveolar / drug effects
Macrophages, Alveolar / immunology*
Macrophages, Alveolar / metabolism
Male
Mannose Receptor
Mannose-Binding Lectins / metabolism
Middle Aged
Monocytes / drug effects
Monocytes / immunology
Monocytes / metabolism
Pulmonary Fibrosis / etiology
Pulmonary Fibrosis / immunology*
Pulmonary Fibrosis / metabolism
Receptors, Cell Surface / metabolism
STAT Transcription Factors / metabolism
Sarcoidosis, Pulmonary / complications
Sarcoidosis, Pulmonary / diagnosis
Sarcoidosis, Pulmonary / metabolism
Scleroderma, Systemic / complications
Scleroderma, Systemic / metabolism
Signal Transduction / drug effects
Signal Transduction / immunology*
Tumor Necrosis Factor-alpha / metabolism
Young Adult

Substances

Chemokines, CC
Cytokines
IL10 protein, human
IL4 protein, human
Interleukin 1 Receptor Antagonist Protein
Interleukin-8
Lectins, C-Type
Mannose Receptor
Mannose-Binding Lectins
Receptors, Cell Surface
STAT Transcription Factors
Tumor Necrosis Factor-alpha
Interleukin-10
Interleukin-4