The potentiating effect of LPS on tumor necrosis factor-alpha production by influenza A virus-infected macrophages.
Infection of murine PU5-1.8 macrophages and human monocytes by influenza A virus was associated with virus replication, release of tumor necrosis factor-alpha (TNF-alpha) and subsequent cell death. In the presence of small and by itself rather inefficient concentrations of lipopolysaccharide (LPS) or free lipid A (1 to 10 ng/ml), TNF-alpha production of virus-infected macrophages was strongly potentiated. LPS-triggered and enhanced TNF-alpha release from virus-infected macrophages was neither due to increased cell survival nor altered virus replication, potentiated TNF-alpha gene transcription, release of intracellularly stored TNF-alpha or shifts in the kinetics of TNF-alpha secretion. Influenza A virus infection alone induced a massive TNF-alpha mRNA accumulation which, however, was only weakly translated into bioactive TNF-alpha protein. When these virus-primed macrophages were exposed to LPS either simultaneously or up to 4 h after infection, an efficient and high translation into TNF-alpha protein occurred. Although the LPS-induced biochemical pathways leading to an augmented TNF-alpha production by virus-infected macrophages still remains unsolved, the findings suggest that the frequently observed serious clinical complications in the course of combined influenza A virus and bacterial infections may be due, at least in part, to an excessive release of cytokines such as TNF-alpha.
Bender
A
A
Institute of Immunology, Philipps University, Marburg, Germany.
Sprenger
H
H
Gong
J H
JH
Henke
A
A
Bolte
G
G
Spengler
H P
HP
Nain
M
M
Gemsa
D
D
D000818:Animals; D016923:Cell Death; D002460:Cell Line; D015232:Dinoprostone / Q000096:biosynthesis; D004591:Electrophoresis, Polyacrylamide Gel; D015870:Gene Expression; D006801:Humans; D015151:Immunoblotting; D009980:Influenza A virus / Q000502:physiology*; D007372:Interferons / Q000096:biosynthesis; D008050:Lipid A / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology*; D008264:Macrophages / Q000276:immunology; D009000:Monocytes / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics; D014779:Virus Replication
D008050:Lipid A; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D007372:Interferons; D015232:Dinoprostone