M2 polarized macrophages in bronchoalveolar lavage of lung transplant recipients

Abstract

Macrophages are the most abundant cells type in the respiratory tract. They can exhibit different polarization based on different signals received: M1 display cytotoxic and pro-inflammatory activities while M2 pro-fibrotic effects (Suji Eapen et al. Scientific Report. 2017: 7: 13392). The latter have been found expanded in small airways of pts with lung fibrosis or asthma (Boorsma et al. Mediators of inflammation. 2013. ID 769214).

Aim of this study was to set up a feasible method to determine degree of M2 polarization on BAL samples and to investigate it in lung transplant recipients.

Cells isolated from BAL were assessed by flow cytometry (FC) (CD14+CD206+ to identify M2 and CD14+CD86+ cells for M1) and by western blot (Arginase-1 and specific for M2). 6 lung transplant recipients were enrolled (within 12 months post transplantation). Two control populations were included (12 IPF patients where M2 expansion is described and 2 Sarcoidosis pts associated to M1 expansion).

Lung recipients showed a significant increase in M2 polarized macrophages by FC (69.97 ± 2.6% vs. 37.35 ± 0.01%; p<0.01 – Fig. 1B), and a 5-fold higher level of Arg-1 compared to sarcoidosis patients (p<0.05 – Fig. 1A). M2 polarization observed in Lung Recipients was analogous to what observed in IPF pts (4.4 fold-increase of Arg-1 levels with respect to sarcoidosis; p<0.05 – Fig. 1A).

M2 polarization is detectable in lung graft early after lung transplantation, also in absence of graft infections or immune complications, possibly as consequence of immunosuppression. This might contribute to later development of late fibrotic complications