title: The expression of functional IL-2 receptor on activated macrophages depends on the stimulus applied.
abstract: Human peripheral blood monocytes (Mo) synthesize prostaglandin E2 (PGE2) when activated with lipopolysaccharide (LPS). This production is strongly enhanced by the addition of supernatant from phytohaemagglutinin (PHA)-activated T cells. To evaluate the factor(s) responsible for this enhancement we studied the effect of several cytokines on the PGE2 metabolism. Recombinant interleukin-1 (IL-1) or recombinant IL-2 strongly enhanced PGE2 synthesis in LPS-stimulated Mo cultures, whereas recombinant interferon-gamma (IFN-gamma) partially inhibited its production. To see whether the effect of IL-2 on Mo was due to the presence of IL-2 receptor (IL-2R) on the cell surface, flow cytometric analysis and electron microscopy were used to investigate IL-2R expression in unstimulated and stimulated Mo. Stimulated, but not resting, Mo displayed the p55 IL-2R chain on their cellular surface and associated with the polyribosomes of the rough endoplasmic reticulum in the cytoplasm. This finding strongly suggested that the p55 chain of the IL-2R was synthesized by activated Mo. To confirm this result, 125I-labelled IL-2 was bound under high- and low-affinity conditions and cross-linked to Mo cultured in the presence of LPS, IFN-gamma or IL-1. The cross-linked 125I-IL-2/IL-2R complexes were analysed by SDS-PAGE. Mo cultured with LPS, IFN-gamma and IL-1 expressed the p55 protein detected by low-affinity cross-linking, whereas only LPS-stimulated Mo displayed a barely detectable band with an apparent MW of 70,000 under high-affinity binding conditions. In addition, stimulated Mo were found capable of producing the soluble form of IL-2R. Finally, LPS-activated Mo only responded to the addition of IL-2 by an increase in PGE2 production, suggesting that the function of IL-2R on activated Mo is linked to the stimulus applied.
authors.affiliation: Department of Human Pathology, Universita' Cattolica S. Cuore, Rome, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Valitutti
authors.forename: A
authors.initials: A
authors.lastname: Carbone
authors.forename: F
authors.initials: F
authors.lastname: Castellino
authors.forename: N
authors.initials: N
authors.lastname: Maggiano
authors.forename: R
authors.initials: R
authors.lastname: Ricci
authors.forename: L M
authors.initials: LM
authors.lastname: Larocca
authors.forename: P
authors.initials: P
authors.lastname: Musiani
mesh_terms: D001685:Biological Factors / Q000494:pharmacology*; D002478:Cells, Cultured; D016207:Cytokines; D015232:Dinoprostone / Q000096:biosynthesis; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D008262:Macrophage Activation; D008264:Macrophages / Q000032:analysis* / Q000187:drug effects / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000032:analysis*; D011994:Recombinant Proteins / Q000494:pharmacology
chemical_list: D001685:Biological Factors; D016207:Cytokines; D007375:Interleukin-1; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins; D015232:Dinoprostone