Bacterial lipoprotein and lipopolysaccharide act synergistically to induce lethal shock and proinflammatory cytokine production.
Septic shock is a major cause of death in the world. Although much is known about the role of LPS in septic shock, little is known about the role of other bacterial components. Lipoprotein (LP) is a major component of bacteria in the family Enterobacteriaceae. LP purified from Escherichia coli was shown to induce TNF-alpha and IL-6 production in peritoneal exudate macrophages obtained from LPS-responsive (C3H/HeOuJ) and LPS-nonresponsive (C3H/HeJ) mice. LP and LPS acted synergistically to induce cytokine production not only in C3H/HeOuJ macrophages but also in C3H/HeJ macrophages. These results suggest that LPS can induce cellular signaling in C3H/HeJ macrophages, and that LPS and LP activate macrophages via different receptors and/or signaling pathways. The role LP plays in septic shock was investigated using the mouse D-galactosamine model. LP induced lethal shock and in vivo production of TNF-alpha and IL-6 in both LPS-responsive and LPS-nonresponsive mice. LPS failed to induce lethal shock or in vivo cytokine production in C3H/HeJ mice. However, LP and LPS acted synergistically in inducing lethal shock and in vivo cytokine production in both LPS-responsive and LPS-nonresponsive mice. Finally, a heat-killed preparation of an E. coli mutant strain that lacked LP was shown to be less efficient than heat-killed wild-type E. coli at inducing lethal shock in C3H/HeJ mice. Collectively, these results suggest that LP and LPS induce cytokine production via different mechanisms and that LP plays an important role in septic shock induced by bacteria in the family Enterobacteriaceae.
Zhang
H
H
Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston 77555-1019, USA.
Peterson
J W
JW
Niesel
D W
DW
Klimpel
G R
GR
D000818:Animals; D004357:Drug Synergism; D004926:Escherichia coli / Q000235:genetics; D005260:Female; D005688:Galactosamine / Q000008:administration & dosage; D007274:Injections, Intraperitoneal; D015850:Interleukin-6 / Q000096:biosynthesis*; D008070:Lipopolysaccharides / Q000633:toxicity*; D008074:Lipoproteins / Q000235:genetics / Q000633:toxicity*; D008262:Macrophage Activation; D051379:Mice; D008809:Mice, Inbred C3H; D009154:Mutation; D012772:Shock, Septic / Q000209:etiology* / Q000276:immunology / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D015850:Interleukin-6; D008070:Lipopolysaccharides; D008074:Lipoproteins; D014409:Tumor Necrosis Factor-alpha; D005688:Galactosamine