Differential expression of genes and receptors in monocytes from patients with cystic fibrosis

Abstract

Introduction: We previously reported defective alternative polarization (M2) of macrophages and early expression of classically polarized (M1) macrophage markers in unpolarized monocyte-derived macrophages (MDMs) in patients with cystic fibrosis (CF). The present study assessed whether the mechanism(s) underlying defective macrophage polarization resided in circulating monocytes.

Methods: Monocyte subsets (classical, intermediate and non-classical), markers for monocyte activation (CD163) and recruitment (CD195), receptors/genes associated with macrophage differentiation and polarization were analyzed in CF and compared with healthy individuals.

Results: No differences were observed in the monocyte subsets or in the expression of CD163 or CD195. Expression of the M-CSF receptor, TLR4, γC, IL-4Rα, IL-13Rα1, TIMP-1 and Cox-2 were higher in CF monocytes, albeit at low levels, whereas, LRP1, MMP9, MMP28 were downregulated compared to mooncytes from healthy individuals.

Conclusions: Our data suggest that differences in CF monocytes may contribute to the reported CFTR-dependent defect in macrophage differentiation, polarization and function.

Keywords: Cox-2; Cystic fibrosis; Gamma-chain receptor; IL-13/IL-4 receptor; IRF4; LRP1; MMP28; MMP9; Macrophage polarization; Monocyte-derived macrophages (MDMs); Monocytes; TIMP-1; TLR4.