Enhanced arachidonic acid metabolism and human neutrophil migration in asthma

Prostaglandins Leukot Essent Fatty Acids. 1990 Oct;41(2):131-8. doi: 10.1016/0952-3278(90)90066-t.

Abstract

In stable state asthmatic patients (AP) without any airway obstruction, the capacity of peripheral blood polymorphonuclear neutrophils (PMN) to produce 5-lipoxygenase metabolites and to migrate, was investigated and compared with the response in healthy subjects (HS). After calcium-ionophore A23187 stimulation, PMN from AP and HS produced LTB4, its hydroxylated derivatives: omega-OH-and omega-CO2H-LTB4) (omega-LTB4, i.e 6-trans-LTB4 and 5,6-diHETE isomers, and 5-HETE. We found an increase in LTB4 (+59%), omega-LTB4 (+39%), 6-trans-LTB4 (+128%), and free 5-HETE (+63%) generation of AP as compared with HS. Unstimulated migration was enhanced in AP (122 +/- 27 PMN/10 high power fields (hpf) in AP versus 74 +/- 25 PMN/10 hpf in HS, p less than 0.025) and suggested a greater capacity of PMN from AP to migrate. This was confirmed by the PAF-induced chemotaxis studies which showed, in AP, a greater PAF-sensitivity of PMN (10(-6) M versus 10(-5) M in HS) and a greater chemotaxis response (600 +/- 50 PMN versus 200 +/- 35 PMN in HS). In AP, we compared the capacity of PMN to generate LTB4 and 5-HETE with their capacity to migrate. We found an inverse correlation (r = 0.86, p less than 0.007) of intracellular free 5-HETE with chemotaxis to PAF.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Arachidonate 5-Lipoxygenase / metabolism*
  • Arachidonic Acid
  • Arachidonic Acids / metabolism*
  • Asthma / metabolism*
  • Calcimycin / pharmacology
  • Chemotaxis, Leukocyte* / drug effects
  • Humans
  • Leukotrienes / biosynthesis*
  • Middle Aged
  • Neutrophils / enzymology
  • Neutrophils / physiology*
  • Platelet Activating Factor / pharmacology

Substances

  • Arachidonic Acids
  • Leukotrienes
  • Platelet Activating Factor
  • Arachidonic Acid
  • Calcimycin
  • Arachidonate 5-Lipoxygenase