TY - JOUR
T1 - Enhanced production of LPS-induced cytokines during differentiation of human monocytes to macrophages
T2 - Role of LPS receptors
AU - Gessani, Sandra
AU - Testa, Ugo
AU - Varano, Barbara
AU - Di Marzio, Paola
AU - Borghi, Paola
AU - Conti, Lucia
AU - Barberi, Tiziano
AU - Tritarelli, Elena
AU - Martucci, Robert
AU - Seripa, Davide
AU - Peschle, Cesare
AU - Belardelli, Filippo
PY - 1993/10/1
Y1 - 1993/10/1
N2 - 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.
AB - 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.
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M3 - Article
C2 - 7690813
AN - SCOPUS:0027270869
VL - 151
SP - 3758
EP - 3766
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 7
ER -