Distinct Properties of Human M-CSF and GM-CSF Monocyte-Derived Macrophages to Simulate Pathological Lung Conditions In Vitro: Application to Systemic and Inflammatory Disorders with Pulmonary Involvement.

Alain Lescoat,Stéphane Jouneau,Laurent Vernhet,Patrick Jégo,Olivier Fardel,Valérie Lecureur,Claudie Morzadec,Yu Augagneur,Alice Ballerie

doi:10.3390/ijms19030894

Abstract

Macrophages play a central role in the pathogenesis of inflammatory and fibrotic lung diseases. However, alveolar macrophages (AM) are poorly available in humans to perform in vitro studies due to a limited access to broncho-alveolar lavage (BAL). In this study, to identify the best alternative in vitro model for human AM, we compared the phenotype of AM obtained from BAL of patients suffering from three lung diseases (lung cancers, sarcoidosis and Systemic Sclerosis (SSc)-associated interstitial lung disease) to human blood monocyte-derived macrophages (MDMs) differentiated with M-CSF or GM-CSF. The expression of eight membrane markers was evaluated by flow cytometry. Globally, AM phenotype was closer to GM-CSF MDMs. However, the expression levels of CD163, CD169, CD204, CD64 and CD36 were significantly higher in SSc-ILD than in lung cancers. Considering the expression of CD204 and CD36, the phenotype of SSc-AM was closer to MDMs, from healthy donors or SSc patients, differentiated by M-CSF rather than GM-CSF. The comparative secretion of IL-6 by SSc-MDMs and SSc-AM is concordant with these phenotypic considerations. Altogether, these results support the M-CSF MDM model as a relevant in vitro alternative to simulate AM in fibrotic disorders such as SSc.

Highlights

Macrophages constitute a heterogeneous population of mononuclear cells
An imbalanced polarization of lung macrophages has been shown to be involved in the pathogenesis of inflammatory interstitial lung diseases (ILD) and systemic conditions with pulmonary involvement [7]
Systemic sclerosis (SSc) is a chronic autoimmune disease characterized by an early inflammation of small vessels followed by fibrotic manifestations such as skin fibrosis and interstitial lung disease with pulmonary fibrosis [10]; the pathogenesis of SSc-associated ILD is still poorly understood

Summary

Introduction

They can adopt various degrees of polarization with distinct functional and phenotypic properties in vivo and in vitro [1] Depending on these polarization characteristics, macrophages can be clustered, on one hand, into pro-inflammatory macrophages, called M1 macrophages or classically activated macrophages [2], and, on the other hand, into alternatively activated macrophages or M2 macrophages, involved in the resolution of inflammation and participating in tissue remodeling [3]. These M1/M2 states of polarization constitute the extreme borders of a wide continuous functional and phenotypic spectrum, reflecting the plasticity and heterogeneity of human macrophages [4,5]. Alveolar macrophages (AM) are involved in the pathogenesis of granulomatous diseases such as sarcoidosis and neoplastic disorders, like lung cancers [1]

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