Stimulating properties of 5-oxo-eicosanoids for human monocytes: synergism with monocyte chemotactic protein-1 and -3

J Immunol. 1996 Nov 15;157(10):4664-71.

Abstract

The newly described products of 5-hydroxyeicosanoid dehydrogenase, 5-oxo-6,8,11,14-eicosatetraenoic acid (ETE) and 5-oxo-15(OH)ETE, induced directional migration and actin polymerization of human monocytes in vitro. At peak concentrations, the two eicosanoids had a chemotactic activity of about 40% of that observed in the presence of an optimal concentration of FMLP and twice the activity elicited by the related eicosanoid 5-hydroxy-6,8,11,14-eicosatetraenoic acid (5-HETE). 15-Oxo-ETE showed a very low but detectable chemotactic activity. All of these chemotactic responses were blocked by Bordetella pertussis toxin, but were resistant to LY255283, a leukotriene B4 (LTB4) receptor antagonist. 5-Oxo-ETEs and 5-HETE induced homologous desensitization of chemotactic response, but did not cross-desensitize to other chemotactic agonists (e.g., monocyte chemotactic protein (MCP)-1 and LTB4). 5-Oxo-ETEs increased in a synergistic fashion the monocyte migration to MCP-1 and MCP-3. In the same range of concentrations, 5-oxo-ETE increased MCP-1-induced release of arachidonic acid from labeled monocytes. No synergistic interaction was observed when FMLP was used as chemoattractant. Thus, this study identifies monocytes as cells responsive to 5-oxo-ETEs and shows that monocyte activation by 5-oxo-ETEs occurs through an LTB4 receptor-independent mechanism that associates with pertussis toxin-sensitive G proteins. The synergistic interaction between 5-oxo-ETEs and C-C chemokines, two families of mediators both synthesized by phagocytic cells, may be relevant in vivo for the regulation of monocyte accumulation at sites of allergic and inflammatory reactions.

Publication types

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

MeSH terms

  • Actins / biosynthesis
  • Arachidonic Acids / metabolism
  • Arachidonic Acids / pharmacology*
  • Chemokine CCL2 / pharmacology*
  • Chemokine CCL7
  • Chemotactic Factors / pharmacology*
  • Chemotaxis, Leukocyte / drug effects
  • Cytokines*
  • Drug Synergism
  • Humans
  • Hydroxyeicosatetraenoic Acids / pharmacology*
  • Macrophage Activation / drug effects
  • Monocyte Chemoattractant Proteins / pharmacology*
  • Monocytes / drug effects*
  • Monocytes / metabolism

Substances

  • Actins
  • Arachidonic Acids
  • CCL7 protein, human
  • Chemokine CCL2
  • Chemokine CCL7
  • Chemotactic Factors
  • Cytokines
  • Hydroxyeicosatetraenoic Acids
  • Monocyte Chemoattractant Proteins
  • 5-oxo-6,8,11,14-eicosatetraenoic acid
  • 5-hydroxy-6,8,11,14-eicosatetraenoic acid