Systemic characterization of macrophage phenotypes from bal fluid of healthy and asthmatic donors

Macrophages are central players in lung pathology with both regulatory and effector properties. Differentially activated macrophages (M1 or M2) may play a role in the pathophysiology of pneumonia and allergy. Recently, microRNAs (miRNAs) have emerged as a regulatory network with great impact on cellular organization and function. We investigate the role of miRNAs in macrophage polarization and associated diseases. Here, we analyzed the systemic microRNA (miRNA) phenotype of alveolar macrophages from asthmatic patients and matched healthy controls.

Bronchial asthma is a chronic inflammatory disease characterized by symptoms in conjunction with paroxysmal occurring bronchospasm. The inflammatory processes in the lungs leading to bronchospasm are complex and not yet fully understood. For this study, we have recruited 20 patients with clinically confirmed bronchial asthma and 20 healthy volunteers. Asthma was diagnosed by symptoms in conjunction with airway hyperresponsiveness (metacholine challenge). Furthermore, the concentration of nitrogen monoxide (FeNO) for all patients and controls was measured. All patients and volunteers underwent a bronchoscopy with bronchoalveolar lavage. The alveolar macrophages were isolated from the lavage fluid by negative selection.

The global miRNA profile was established by TaqMan Low Density Array. We identified a set of miRNAs that was regulated in an asthma-dependent way (FeNO > 30), and we performed in silico target prediction with these candidates. This analysis identified HIF1alpha as a putative target of miR-18a and miR-210 which were both regulated in the context of asthma.

The involvement of HIF1alpha as a central transcription factor in macrophage polarization will be further analyzed with respect to asthma pathogenesis.