Oxidoreductases in Lipoxin A4 Metabolic Inactivation. A Novel Role for 15-oxoprostaglandin 13-reductase/leukotriene B4 12-hydroxydehydrogenase in Inflammation

The lipoxins (LX) are autacoids that act within a local inflammatory milieu to dampen neutrophil recruitment and promote resolution. 15-Hydroxyprostaglandin dehydrogenase (15-PGDH) and 15-oxoprostaglandin 13-re-ductase, also termed leukotriene B 4 12-hydroxydehydro- genase (PGR/LTB 4 DH), are two enzymatic activities appreciated for their roles in the metabolism of prostaglandins and LTB 4 . Here, we determined whether these oxidoreductases also catalyze the conversion of lipoxin A 4 (LXA 4 ) and assessed the activities of these LXA 4 me- tabolites. 15-Oxo-LXA 4 was generated by incubating LXA 4 with 15-PGDH and NAD 1 for studies of its further conversion. PGR/LTB 4 DH catalyzed the NADH-depend- ent reduction of 15-oxo-LXA 4 to yield 13,14-dihydro-15-oxo-LXA 4 . With NADH as a cofactor, 15-PGDH acted as a 15-carbonyl reductase and catalyzed the conversion of 13,14-dihydro-15-oxo-LXA