Figure 1.

(A) Initial metabolic step of LXA₄ inactivation in mouse whole blood and 15-oxo-LXA₄ MS/MS spectrum. LXA₄ (21 μM) was incubated ex vivo in mouse whole blood for 3 hr. The MS/MS spectrum of the major oxo-product is indicative of 15-oxo-LXA₄, with diagnostic product ions at m/z: 349 (a = [M-H]⁻), 331 (a - H₂O), 313 (a - 2H₂O), 305 (b = [M-H]⁻ - CO₂), 287 (b - H₂O), 269 (b - 2H₂O), 233 (c), and 217 (c - O). (B) Biostability of LXA₄ and stable analogs in mouse whole blood. LXA₄, ATLa₁, which carries a racemic methyl group at C-15, and 15-epi-16-(para-fluoro)-phenoxy-LXA₄ [ATLa₂, in which a bulky (para-fluoro)-phenoxy group replaces the ω-chain at C-16] were added (see Materials and Methods) to heparinized mouse whole blood and incubated at 37°C for 0 and 3 hr. After centrifugation at 800 × g and 0°C, the plasma supernatants were drawn off and stopped in two volumes of ice-cold methanol. The lipoxins were extracted by solid phase methodology and quantitated by LC/MS/MS. Values represent mean ± SEM (n = 3–4).