Alveolar lining fluid regulates mononuclear phagocyte 5-lipoxygenase metabolism

The enzyme 5-lipoxygenase (5-LO) catalyses the synthesis of leukotrienes (L T), which are important in phagocytosis and killing of microorganisms, The alveolar macrophage (AM), the primary resident defender of the alveolar spa ce, has a greater capacity for LT synthesis than its precursor, the periphe ral blood monocyte (PBM), This study investigated whether the alveolar lini ng fluid (ALF) upregulates LT synthetic capacity in mononuclear phagocytes, Rat AM, peritoneal macrophages (PM) and ALF were obtained hy lavage from pa thogen-free animals, Human PBM were isolated from normal subjects. 5-LO met abolism and expression were measured with and without ALF. Rat ALF increased 5-LO metabolism (136.4+/-15.1% of control) in cultured PB M, This was associated with increased 5-LO activating protein (FLAP) (357+/ -29.5%), and 5-LO expression (188+/-31.3%). Culture of AM for 3 days result ed in a greater decrement in LTB4 synthesis (LTB4 15.4+/-6.9% of day 1) tha n in PM (54.7+/-8.3% of day 1), suggesting a greater dependence of AM 5-LO metabolism on ALF. 5-LO and FLAP expression decreased to a greater degree i n AM than PM in culture, Furthermore, AM cultured with ALF maintained their LT synthetic capacity, FLAP and 5-LO expression compared with control cell s cultured in medium alone. In conclusion, alveolar lining fluid increased 5-lipoxygenase metabolism in peripheral blood monocytes and maintained it in cultured alveolar macropha ges, by a mechanism of increased 5-lipoxygenase and 5-lipoxygenase activati ng protein expression. This may boost host defence capabilities.