Enhanced production of LPS-induced cytokines during differentiation of human monocytes to macrophages: Role of LPS receptors

Sandra Gessani, Ugo Testa, Barbara Varano, Paola Di Marzio, Paola Borghi, Lucia Conti, Tiziano Barberi, Elena Tritarelli, Robert Martucci, Davide Seripa, Cesare Peschle, Filippo Belardelli

Research output: Contribution to journalArticlepeer-review

Abstract

In vitro cultivated human monocytes isolated from normal peripheral blood show a time-dependent differentiation into macrophages characterized by an increased expression of transferrin receptors, CD11/CD18, and CD14 Ag. We measured the secretion of TNF-α and IL-6 in freshly isolated monocytes and in differentiated macrophages after LPS treatment. Differentiated macrophages produced significantly higher amounts of TNF-α and IL-6 than freshly isolated monocytes. This increased secretion was not a result of an enhanced accumulation of TNF-α and IL-6 mRNA, as comparative levels of these transcripts were found in both cell types after LPS treatment. Furthermore, LPS did not induce an antiviral state to VSV3 in monocytes, but it reduced by 3 to 5 log10 the virus yield in differentiated macrophages. The addition of antibodies to IFN-β completely inhibited the LPS-induced antiviral state to VSV, but antibodies to IFN-α, TNF-α, or IL-6 were ineffective. A marked accumulation of IFN-β mRNA was found in both cell types after LPS treatment. Binding experiments with FITC-LPS revealed a slightly higher overall binding affinity for LPS in freshly explanted monocytes as compared with differentiated macrophages, even though the maximal binding was higher in macrophages. In both cell types, the LPS binding was partially inhibited by antibodies to CD14. These results demonstrate that: 1) in vitro differentiation of human monocytes to macrophages leads to an enhanced LPS response in terms of (a) progressive increase of IL-6/TNF-α production and (b) acquisition of an IFN-β mediated antiviral state; 2) this enhanced response to LPS, largely CD14-independent, is not linked to any increased accumulation of cytokine mRNA, but is probably a result of an increased synthesis and/or secretion of these cytokines.

Original languageEnglish
Pages (from-to)3758-3766
Number of pages9
JournalJournal of Immunology
Volume151
Issue number7
Publication statusPublished - Oct 1 1993

ASJC Scopus subject areas

  • Immunology

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