Inhibition of leukotriene B4-induced neutrophil migration by lipoxin A4: structure-function relationships

Biochem Biophys Res Commun. 1991 Nov 14;180(3):1416-21. doi: 10.1016/s0006-291x(05)81354-3.

Abstract

Lipoxins are trihydroxytetraene metabolites which are derived from arachidonic acid through an interaction between different lipoxygenase pathways. Previous work has shown that lipoxin A4 (LXA4) inhibits the chemotactic responsiveness of neutrophils (PMN) to leukotriene B4. We have now assessed the structural determinants of the lipoxin A4 molecule which are necessary for its inhibitory activity, using structural analogs of LXA4 prepared by chemical synthesis. Our results indicate the importance of two adjacent free hydroxyl groups in either the R or the S configuration; one hydroxyl group has to be in the C-6 position, but the other hydroxyl group can be in either the C-5 or the C-7 position for the conferment of inhibitory activity.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chemotaxis, Leukocyte / drug effects*
  • Humans
  • Hydroxyeicosatetraenoic Acids / chemical synthesis
  • Hydroxyeicosatetraenoic Acids / pharmacology*
  • In Vitro Techniques
  • Kinetics
  • Leukotriene B4 / antagonists & inhibitors
  • Leukotriene B4 / pharmacology*
  • Lipoxins*
  • Molecular Structure
  • Neutrophils / drug effects
  • Neutrophils / physiology*
  • Structure-Activity Relationship

Substances

  • Hydroxyeicosatetraenoic Acids
  • Lipoxins
  • lipoxin A4
  • Leukotriene B4