Specific inhibition of leukotriene B4 (LTB4)-induced neutrophil emigration by 20-hydroxy LTB4: implications for the regulation of inflammatory responses

Br J Pharmacol. 1993 Sep;110(1):423-7. doi: 10.1111/j.1476-5381.1993.tb13827.x.


1. The interaction between leukotriene B4 (LTB4) and its metabolite, 20-hydroxy LTB4 in the control of neutrophil emigration was examined in guinea-pig skin. 2. Leukotriene B4 (10-300 ng) elicited a dose-dependent increase in neutrophil infiltration (as measured by myeloperoxidase activity) 4 h after injection into guinea-pig skin. In contrast, 20-hydroxy LTB4 (30-1000 ng) displayed only weak inflammatory activity in this assay. 3. Although 20-hydroxy LTB4 had low agonist activity, this metabolite caused a potent dose-dependent inhibition of responses to LTB4 (100 ng), when administered systemically (ED50 = 1.3 micrograms kg-1, s.c.) without significantly affecting neutrophil infiltration in response to C5a (2 micrograms). Systemic administration of 20-carboxy LTB4 (10 micrograms) did not affect neutrophil accumulation in response to LTB4 or C5a. In addition, neither 15(S)-hydroxy 5(S)-HPETE(10 micrograms) nor lipoxin A4 (10 micrograms) inhibited responses to LTB4. 4. Addition of 20-hydroxy LTB4 (10(-11)-10(-8) M) to human blood prior to isolation of the neutrophils led to concentration-dependent decrease in the number of LTB4 receptors and decreased chemotactic responsiveness to LTB4 without affecting responses to C5a. Incubation of blood with 20-carboxy LTB4 (10(-8) M) did not reduce LTB4 receptor number of chemotactic responsiveness to LTB4. 5. These data indicate that although 20-hydroxy LTB4 is a weak agonist at LTB4 receptors, it can desensitize neutrophils to the effects of LTB4 via down-regulation of the high affinity receptor and thus provides evidence for a mechanism whereby inflammatory responses may be regulated.

MeSH terms

  • Animals
  • Chemotaxis, Leukocyte / drug effects*
  • Guinea Pigs
  • In Vitro Techniques
  • Inflammation / chemically induced
  • Inflammation / pathology*
  • Injections, Intradermal
  • Leukotriene B4 / administration & dosage
  • Leukotriene B4 / analogs & derivatives*
  • Leukotriene B4 / antagonists & inhibitors*
  • Leukotriene B4 / pharmacology
  • Male
  • Neutrophils / drug effects
  • Peroxidase / metabolism
  • Receptors, Leukotriene / drug effects
  • Skin / enzymology


  • Receptors, Leukotriene
  • Leukotriene B4
  • 5,12,20-trihydroxy-6,8,10,14-eicosatetraenoic acid
  • Peroxidase