Effects of two leukotriene B4 (LTB4) receptor antagonists (LY255283 and SC-41930) on LTB4-induced human neutrophil adhesion and superoxide production

Prostaglandins Leukot Essent Fatty Acids. 1991 Aug;43(4):267-71. doi: 10.1016/0952-3278(91)90041-3.

Abstract

Leukotriene B4 (LTB4) induces a number of functional changes in human neutrophils, including both superoxide release and CD11b/CD18 (Mo1)-mediated adherence to various substrates, such as keyhole limpet hemocyanin (KLH). These effects are both time- and concentration-dependent. Neutrophil adhesion was at least 10-fold more sensitive to the stimulatory action of LTB4 than superoxide production. Two LTB4 receptor antagonists, LY255283 (1-(5-ethyl-2-hydroxy-4-(6-methyl-6-(1H-tetrazol-5-yl)heptyloxy )- phenyl)ethanone) and the sodium salt of SC-41930 (7-[3-(4-acetyl-3-methoxy-2-propylphenoxy)-propoxy]-3,4-dihydro-8- propyl-2H- 1-benzopyran-2-carboxylic acid) were evaluated for effects on human neutrophil superoxide production and adhesion. Despite being more sensitive to LTB4-induced stimulation, neutrophil adhesion was at least 100-fold less sensitive to inhibition by LY255283 and SC-41930 than superoxide production. Both LTB4 receptor antagonists behaved similarly in these models. These compounds did not inhibit neutrophil responses induced by granulocyte/macrophage colony-stimulating factor (GM-CSF).

MeSH terms

  • Adult
  • Benzopyrans / pharmacology
  • Cell Adhesion / drug effects
  • Humans
  • In Vitro Techniques
  • Leukotriene B4 / blood
  • Leukotriene B4 / pharmacology*
  • Neutrophils / drug effects*
  • Neutrophils / physiology
  • Receptors, Immunologic / antagonists & inhibitors*
  • Receptors, Immunologic / metabolism
  • Receptors, Leukotriene B4
  • Superoxides / blood
  • Tetrazoles / pharmacology

Substances

  • Benzopyrans
  • Receptors, Immunologic
  • Receptors, Leukotriene B4
  • Tetrazoles
  • Superoxides
  • SC 41930
  • Leukotriene B4
  • LY 255283