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 LTB 4, its hydroxylated derivatives: ω-OH- and ω-CO 2H-LTB 4) (ω-LTB 4, i.e 6-trans-LTB 4 and 5,6-diHETE isomers, and 5-HETE. We found an increase in LTB 4 (+59%), ω-LTB 4 (+39%), 6-trans-LTB 4 (+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 < 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 LTB 4 and 5-HETE with their capacity to migrate. We found an inverse correlation (r = 0.86, p < 0.007) of intracellular free 5-HETE with chemotaxis to PAF.
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