title: 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.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors: Division of Basic Science, Institute of Human Virology, Baltimore, Maryland 21201, USA. hone@umbi.umd.edu
authors: D M
authors: DM
authors: Hone
authors: J
authors: J
authors: Powell
authors: R W
authors: RW
authors: Crowley
authors: D
authors: D
authors: Maneval
authors: G K
authors: GK
authors: Lewis
mesh_terms: D054405:Chemokine CCL3; D054407:Chemokine CCL4; D004926:Escherichia coli / Q000737:chemistry* / Q000235:genetics; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D019402:Macrophage Inflammatory Proteins / Q000378:metabolism*; D009154:Mutation; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D054405:Chemokine CCL3; D054407:Chemokine CCL4; D007375:Interleukin-1; D008070:Lipopolysaccharides; D019402:Macrophage Inflammatory Proteins; D014409:Tumor Necrosis Factor-alpha