Lipopolysaccharide from an Escherichia coli htrB msbB mutant induces high levels of MIP-1 alpha and MIP-1 beta secretion without inducing TNF-alpha and IL-1 beta

J Hum Virol. 1998 May-Jun;1(4):251-6.


Objective: To identify a lipopolysaccharide (LPS) that retains the capacity to induce beta-chemokine secretion without the concomitant activation of pyrogenic cytokines.

Methods: LPS was extracted from strain MLK986 (mLPS), an htrB1::Tn10, msbB::ocam mutant of Escherichia coli that is defective for lipid A synthesis, and from wild-type parent E coli strains, W3110 (wtLPS). The capacity of these LPS preparations to induce tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and macrophage inflammatory proteins 1 alpha (MIP-1 alpha) and MIP-1 beta was assessed using a human peripheral blood mononuclear cell (PBMC) activation assay.

Results: Stimulation of PBMCs with mLPS did not induce measurable levels of pyrogenic cytokines TNF-alpha and IL-1 beta, whereas wtLPS induced high levels of these cytokines. Furthermore, mLPS antagonized the induction of TNF-alpha secretion by wtLPS. Nonetheless, mLPS retained a discrete agonist activity that induced MIP-1 alpha and MIP-1 beta secretion by PBMCs. This latter agonist activity appears to be unique to mLPS, since two previously documented LPS antagonists, Rhodobacter sphaeroides diphosphoryl lipid A and synthetic lipid IVA, did not induce MIP-1 alpha and MIP-1 beta secretion. Furthermore, synthetic lipid IVA was an antagonist of MIP-1 alpha and MIP-1 beta induction by mLPS.

Conclusion: These results show that mLPS exhibits a novel bipartite activity, being an effective antagonist of TNF-alpha induction by wtLPS, while paradoxically being an agonist of MIP-1 alpha and MIP-1 beta secretion.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Chemokine CCL3
  • Chemokine CCL4
  • Escherichia coli / chemistry*
  • Escherichia coli / genetics
  • Humans
  • Interleukin-1 / metabolism
  • Leukocytes, Mononuclear / drug effects*
  • Lipopolysaccharides / pharmacology*
  • Macrophage Inflammatory Proteins / metabolism*
  • Mutation
  • Time Factors
  • Tumor Necrosis Factor-alpha / metabolism


  • Chemokine CCL3
  • Chemokine CCL4
  • Interleukin-1
  • Lipopolysaccharides
  • Macrophage Inflammatory Proteins
  • Tumor Necrosis Factor-alpha