HUMAN ALVEOLAR MACROPHAGES HAVE 15-LIPOXYGENASE AND GENERATE 15(S)-HYDROXY-5,8,11-CIS-13-TRANS-EICOSATETRAENOIC ACID AND LIPOXINS

Eicosanoids derived from lipoxygenase (LO)-catalyzed reactions play im portant roles in pulmonary inflammation. Here, we examined formation o f LO-derived products by human alveolar macrophages (HAM). HAM convert ed [1-C-14]arachidonic acid to a product carrying C-14-radiolabel that was identified as 15(S)-hydroxy-5,8,11-cis-13-trans-eicosatetraenoic acid (15-HETE) by physical methods. 15-LO mRNA was demonstrated in HAM by reverse transcription-polymerase chain reaction. Incubation of HAM for 3 d with interleukin 4 (IL-4) before exposure to [1-C-14]arachido nic acid led to both increased mRNA for 15-LO and a 4-fold increase in 15-HETE formation. In contrast, 5(S)-hydroxy-6-trans-8,11,14-cis-eico satetraenoic acid generation was not significantly altered by prior ex posure to IL-4. Additionally, lipoxins (LXA4 and LXB4) were detected f rom endogenous substrate, albeit in lower levels than leukotriene B4 ( LTB4), in electrochemical detection/high performance liquid chromatogr aphy profiles from HAM incubated in the presence and absence of the ch emotactic peptide (FMLP) or the calcium ionophore (A23187). Exposure o f HAM to leukotriene A4 (LTA4) resulted in a 2-fold increase in LXA4 a nd 10-fold increase in LXB4. These results demonstrate the presence of 15-LO mRNA and enzyme activity in HAM and the production of LXA4 and LXB4 by these cells. Along with 5-LO-derived products, the biosynthesi s of 15-LO-derived eicosanoids by HAM may also be relevant in modulati ng inflammatory responses in the lung.