N-formyl-methionyl-leucyl-phenylalanine (FMLP) inhibits the interferon-g induced expression of FcgRI on human monocytes.

BEIGIER-BOMPADRE, MACARENA; BARRIONUEVO, PAULA; ALVES-ROSA, FERNANDA; PALERMO, MARINA; ISTURIZ, MARTÍN

Punta del Este, Uruguay.

Congreso; Vº Congreso Latinoamericano de Inmunología.; 1999

Asociación Latinoamericana de Inmunología (ALAI).

   Cell surface receptors for the Fc portion of IgG (FcgRs) play important roles in immune and inflammatory responses. The high affinity receptor FcgRI is capable of mediating phagocytosis, clearance of immune complexes, respiratory burst, antibody-dependent cell-mediated cytotoxicity (ADCC) and secretion of inflammatory cytokines. Previously, we have shown that FMLP, a powerful chemotactic agent, induces a profound down regulation of FcgRs in human neutrophils. The activation of monocyte/macrophages by interferon-g (IFN-g) is characterized by a pronounced increase in FcgRI, and consequently many FcgRI-dependent functions. In this study we investigated the effect of FMLP on the induction of FcgRI by IFN-g, using human mononuclear cells. Other IFN-g modulated functions were also studied. FcgRI was significantly up-regulated by human recombinant IFN-g (200 U/ml) after 24 h of incubation. FMLP in a concentration of 1x10-6M did not modify the FcgRI expression. However, one hour of pretreatment with FMLP induced a drastic inhibition of the FcgRI up-regulation induced by IFN-g. The expression of FcgRI was evaluated by flow cytometry using a monoclonal antibody anti-CD64 (anti-FcgRI) and monocytes were identified as CD14 positive cells. The results are expressed as % of control, MIF ± SEM: a)FMLP: 96 ± 2; b)IFN-g: 238 ± 32; c)FMLP + IFN-g: 130 ± 12; n=12; b) vs c) p<0.001 (Wilcoxon test, two tails). The effect of FMLP was also observed with concentrations of 1x10-7 and 1x10-8M. In order to investigate whether the inhibition of FcgRI up-regulation correlated with FcgRI-dependent functions, ADCC was evaluated. The results of the ADCC are shown as % of control ± SD in a representative experiment: a)FMLP: 112 ± 69; b)IFN-g: 467 ± 15; c)FMLP + IFN-g: 120 ± 24 ;n=5; b) vs c) p<0.001 (Wilcoxon test, two tails). The non adherent population from these mononuclear cells (mostly NK and other CD14 negative cells) was not modulated by FMLP. These results were obtained with different cell donors, in spite of the variability attributed to intrinsic susceptibility to FMLP or IFN-g, and/or to the heterogeneity of monocyte subpopulations. IFN-g also enhances the expression of class II antigens and the secretion of TNF-a in human monocytes but these effects were not modulated by FMLP. These results demonstrate that formylated peptides has to be considered as important regulatory molecules in inflammatory mechanisms due to bacterial infections.