The formyl peptide N-formyl-methionyl-leucyl-phenylalanine downregulates the expression of FcgammaRs in interferon-gamma-activated monocytes/macrophages in vitro and in vivo.
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. FcgammaRI is a receptor for the Fc portion of immunoglobulin G expressed in monocytes that mediates cytotoxicity and is upregulated by interferon-gamma (IFN-gamma) and interleukin-10 (IL-10). In this report, we demonstrate that N-formyl-methionyl-leucyl-phenylalanine (FMLP) downregulates the expression of FcgammaRI in IFN-gamma-treated monocytes, but not in IL-10-treated monocytes. We determine that supernatants obtained from monocytes treated with IFN-gamma and then exposed to FMLP induce the downregulation of FcgammaRI 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 FcgammaRI, when added to naïve monocytes. Similar observations were obtained in vivo in a mouse model of chronic inflammation. In vivo, FMLP also downregulates the expression of FcgammaRs in IFN-gamma-activated macrophages. Our results support the existence of a new mechanism through which FMLP could modulate the activity of monocytes/macrophages during bacterial infections.
Beigier-Bompadre
M
M
CONICET, División Inmunología, Instituto de Investigaciones Hematológicas, Academia Nacional de Medicina, Buenos Aires, Argentina. mbeigier@yahoo.com
Barrionuevo
P
P
Alves-Rosa
F
F
Rubel
C J
CJ
Palermo
M S
MS
Isturiz
M A
MA
D000818:Animals; D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D007371:Interferon-gamma / Q000276:immunology* / Q000494:pharmacology; D016753:Interleukin-10 / Q000276:immunology; D008262:Macrophage Activation / Q000187:drug effects / Q000276:immunology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009000:Monocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000276:immunology* / Q000494:pharmacology; D011480:Protease Inhibitors / Q000494:pharmacology; D017452:Receptors, IgG / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000276:immunology
D011480:Protease Inhibitors; D017452:Receptors, IgG; D016753:Interleukin-10; D009240:N-Formylmethionine Leucyl-Phenylalanine; D007371:Interferon-gamma