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 > 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.
MOUSE MACROPHAGE CLONES IMMORTALIZED BY RETROVIRUSES ARE FUNCTIONALLY HETEROGENEOUS
RIGHI M;
1991
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 > 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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.