title: Mouse macrophage clones immortalized by retroviruses are functionally heterogeneous.
abstract: Murine macrophage clones were generated from thymus, spleen, brain, and bone marrow by in vitro immortalization with recombinant retroviruses carrying an avian v-myc oncogene. The cloned cell lines express F4/80 molecules, exert phagocytosis, have nonspecific esterase activity, and express class II molecules after interferon gamma activation. The macrophage clones are diploid and their karyotypes have remained stable for greater than 3 years in culture. After the macrophage clones were activated, their pattern of cytokine production was investigated. Functional heterogeneity in cytokine transcription was demonstrated: one of six liposaccharide-activated macrophages was unable to transcribe interleukin 1 alpha, whereas all of the liposaccharide-activated clones were able to transcribe tumor necrosis factor alpha. Interleukin 6 production was detected in three of six clones. The production of nitrite and tumor necrosis factor alpha as effector molecules of cytotoxicity was detected in all clones, thus showing that a single macrophage can exert more than one cytotoxic mechanism. The results indicate that immortalized and cloned macrophages have a differentially regulated expression of cytokine genes, adding further evidence for the existence of functional heterogeneity among cloned macrophages. This heterogeneity seems to derive from differentiation-related mechanisms rather than from external constraints.
authors.affiliation: Consiglio Nazionale Ricerche Center of Cytopharmacology, Milan, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Pirami
authors.forename: B
authors.initials: B
authors.lastname: Stockinger
authors.forename: S B
authors.initials: SB
authors.lastname: Corradin
authors.forename: M
authors.initials: M
authors.lastname: Sironi
authors.forename: M
authors.initials: M
authors.lastname: Sassano
authors.forename: P
authors.initials: P
authors.lastname: Valsasnini
authors.forename: M
authors.initials: M
authors.lastname: Righi
authors.forename: P
authors.initials: P
authors.lastname: Ricciardi-Castagnoli
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D001853:Bone Marrow / Q000276:immunology; D001921:Brain / Q000276:immunology; D002462:Cell Membrane / Q000276:immunology; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D002999:Clone Cells; D003602:Cytotoxicity, Immunologic; D005455:Fluorescent Antibody Technique; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D007375:Interleukin-1 / Q000235:genetics; D015850:Interleukin-6 / Q000096:biosynthesis; D007621:Karyotyping; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D009573:Nitrites / Q000378:metabolism; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D012190:Retroviridae / Q000235:genetics*; D013154:Spleen / Q000276:immunology; D013950:Thymus Gland / Q000276:immunology; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D000949:Histocompatibility Antigens Class II; D007375:Interleukin-1; D015850:Interleukin-6; D009573:Nitrites; D014409:Tumor Necrosis Factor-alpha; D012313:RNA