Arachidonate 5-lipoxygenase metabolism in human neutrophils from patients with asthma: in vitro effect of nedocromil sodium

Int Arch Allergy Immunol. 1992;97(3):209-15. doi: 10.1159/000236121.

Abstract

Among the cells which participate in amplification of the local inflammatory reaction in asthma, neutrophils (PMN) are pro-inflammatory cells that can generate inflammatory mediators and arachidonic acid derivatives in particular. In asthmatic patients (AP) with attacks, the capacity of blood PMN to produce 5-lipoxygenase metabolites was investigated and compared to the response in healthy subjects (HS). PMN from 6 AP and from 6 HS were stimulated by calcium ionophore A23187 and arachidonate 5-lipoxygenase metabolites were analyzed by reverse-phase HPLC. LTB4, 6-trans LTB4, omega OH-LTB4 and 5-HETE were identified. In AP, total LTB4 synthesis was enhanced as compared to synthesis with PMN in HS. But the total 5-HETE synthesis by PMN from AP was decreased. Thus, the inflammatory potential of PMN from AP was enhanced in comparison to HS. The anti-inflammatory effect of nedocromil sodium (NS) was studied in the 5-lipoxygenase metabolism of arachidonic acid. NS (10(-4) mol/l) inhibited total LTB4 synthesized by PMN in AP but not in HS. We conclude that NS affects leukotriene synthesis only in cells with enhanced inflammatory potential.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Arachidonate 5-Lipoxygenase / metabolism*
  • Asthma / drug therapy*
  • Calcimycin
  • Chromatography, High Pressure Liquid
  • Humans
  • Hydroxyeicosatetraenoic Acids / biosynthesis
  • In Vitro Techniques
  • Leukotriene B4 / biosynthesis
  • Male
  • Middle Aged
  • Nedocromil
  • Neutrophils / metabolism*
  • Quinolones / pharmacology*

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Hydroxyeicosatetraenoic Acids
  • Quinolones
  • Nedocromil
  • Leukotriene B4
  • Calcimycin
  • 5-hydroxy-6,8,11,14-eicosatetraenoic acid
  • Arachidonate 5-Lipoxygenase