Lipopolysaccharide and phorbol 12-myristate 13-acetate both impair monocyte differentiation, relating cellular function to virus susceptibility.
Both lipopolysaccharide (LPS) and phorbol 12-myristate 13-acetate (PMA) impeded monocyte to macrophage differentiation with respect to typical phenotypic modulation and certain phagocyte-related processes. The down-regulation of the porcine monocyte marker SWC1, and up-regulation of the SWC9 macrophage marker were retarded, but not inhibited, as was the differentiation-associated down-regulation of p53 and myeloperoxidase. Despite this clear impairment of macrophage differentiation, not all cellular functions were equally susceptible. Both agents inhibited phagocytosis, but not low-density lipoprotein receptor-associated endocytosis. Only LPS inhibited tartrate-resistant acid phosphatase up-regulation. In contrast, increase of vacuolar acidification rates was more susceptible to PMA. The activity of certain endosomal/lysosomal enzymes - esterase, nucleotidase, peroxidase and cathepsins - was generally enhanced by both LPS and PMA. This contrasted with autophagosomal activity, detected through the induction of an antiviral state. Disruption of autophagosomes and lysosomes (methionine-O-methyl ester), but not lysosomes alone (glycyl-L-phenylalanine) reversed LPS-induced inhibition of virus replication, without influencing the PMA-induced antiviral effect. Thus, PMA is similar to LPS in inhibiting monocyte to macrophage differentiation, when primary blood monocytes are employed, but not all pathways are equally susceptible. The analyses demonstrate that the pathways modulated during monocyte differentiation function somewhat independently. Moreover, certain functions of monocytic cells are more important with respect to the outcome of virus infection, with autophagosomal activities in particular favouring cell survival.
Basta
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Institute of Virology and Immunoprophylaxis, Mittelhäusern, Switzerland.
Knoetig
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S
Summerfield
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McCullough
K C
KC
D000358:African Swine Fever Virus / Q000502:physiology; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D006691:Classical Swine Fever / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D004198:Disease Susceptibility; D011992:Endosomes / Q000201:enzymology; D006863:Hydrogen-Ion Concentration; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008247:Lysosomes / Q000201:enzymology; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology / Q000821:virology; D010587:Phagocytosis / Q000187:drug effects; D013552:Swine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014779:Virus Replication
D016207:Cytokines; D008070:Lipopolysaccharides; D013755:Tetradecanoylphorbol Acetate