Enhanced arachidonic acid metabolism and human neutrophil migration in asthma.
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.
Radeau
T
T
INSERM U 58, Montpellier, France.
Chavis
C
C
Damon
M
M
Michel
F B
FB
Crastes de Paulet
A
A
Godard
P H
PH
D000293:Adolescent; D000328:Adult; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism*; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D001249:Asthma / Q000378:metabolism*; D000001:Calcimycin / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D006801:Humans; D015289:Leukotrienes / Q000096:biosynthesis*; D008875:Middle Aged; D009504:Neutrophils / Q000201:enzymology / Q000502:physiology*; D010972:Platelet Activating Factor / Q000494:pharmacology
D001095:Arachidonic Acids; D015289:Leukotrienes; D010972:Platelet Activating Factor; D016718:Arachidonic Acid; D000001:Calcimycin; D001094:Arachidonate 5-Lipoxygenase