The formyl peptide N-formyl-methionyl-leucyl-phenylalanine downregulates the expression of FcγRs in interferon-γ-activated monocytes/macrophages in vitro and in vivo

Abstract

N-Formyl peptides are cleavage products of bacterial and mitochondrial proteins that have pro-inflammatory activities and play an important role in antibacterial host defence. FcγRI is a receptor for the Fc portion of immunoglobulin G expressed in monocytes that mediates cytotoxicity and is upregulated by interferon-γ (IFN-γ) and interleukin-10 (IL-10). In this report, we demonstrate that N-formyl-methionyl-leucyl-phenylalanine (FMLP) downregulates the expression of FcγRI in IFN-γ-treated monocytes, but not in IL-10-treated monocytes. We determine that supernatants obtained from monocytes treated with IFN-γ and then exposed to FMLP induce the downregulation of FcγRI in naïve monocytes. This effect is abrogated by the protease inhibitors phenylmethylsulphonyl fluoride and phosphoramidon, which inhibit serine and metalloproteases, respectively. Supernatants from FMLP-treated neutrophils also induce the downregulation of FcγRI, when added to naïve monocytes. Similar observations were obtained in vivo in a mouse model of chronic inflammation. In vivo, FMLP also down-regulates the expression of FcγRs in IFN-γ-activated macrophages. Our results support the existence of a new mechanism through which FMLP could modulate the activity of monocytes/macrophages during bacterial infections.