Revisiting cross-tolerance with highly purified LPS

• Published in: Journal of endotoxin research 2004-01, Vol.10 (5), p.203-203
• Main Authors: Fitting, C, Adib-Conquy, M, Tirsoaga, A, Caroff, M, Cavaillon, J-M
• Format: Article
• Language: English
• Subjects: Escherichia coli
• ISSN: 0968-0519

Knowledge about endotoxin tolerance and cross-tolerance between LPS and different TLR ligands have been essentially achieved with conventional LPS, extracted according to the Westphal's method, and purified according conventional methods. However, more recent investigations with highly purified LPS led to contradictory results. We compared the cross-tolerance phenomenon with conventional Escherichia coli LPS (Sigma) and a highly purified E. coli LPS. We ensured that conventional LPS activates both peritoneal macrophages from TLR2 super(-/-) and TLR4 super(-/-) mice while highly purified LPS was only active on TLR2 super(-/-) macrophages. Human monocytes were pre-treated overnight with TLR ligands (tolerization), washed and challenged for the next 24 h with TLR ligands and TNF production was assessed in the supernatants. Conventional LPS was tolerizing human monocytes for a further challenge with both LPS. In contrast, highly purified LPS had (depending upon concentrations) weak or no capacity to tolerize monocytes to a challenge with conventional LPS. Pre-treatment of human monocytes with specific TLR2 ligands (Pam sub(3)CysSK sub(4) or Pam sub(2)CysSK sub(4)) moderately tolerized human monocytes to both LPSs. In contrast, pre-treatment with conventional and highly purified LPS led to divergent results in response to a challenge with TLR2 ligands.