Enhanced 5-lipoxygenase activity in lung macrophages compared to monocytes from normal subjects

We compared lipoxygenase activities of lung macrophages obtained from bronchoalveolar lavage to activities of blood monocytes purified by using discontinuous plasma/Percoll density gradients and adherence to tissue culture plastic in five normal subjects. Cells were incubated with ionophore A23187 (10^-9 to 10^-5 M) or arachidonic acid (0.12 to 80 μM) for 1 to 60 min at 37°C to construct dose-response and time-dependent curves of lipoxygenase product generation. Products were identified and were quantified by using high-pressure liquid chromatography and ultraviolet spectroscopy. Under all conditions of product generation, both macrophages and monocytes generated predominantly (5S-12R)-dihydroxy-(6Z,8E,10E,14Z)-eicosatetraenoic acid (leukotriene B₄ (LTB₄)) and (5S)-hydroxy-(6E,8Z,11Z,14Z)-eicosatetraenoic acid (5-HETE), but, in each subject, macrophages invariably released greater amounts of LTB₄ and 5-HETE than monocytes. In response to A23187, macrophages released a maximum of 183 ± 96 pmol of LTB₄ and 168 ± 108 pmol of 5-HETE per 10⁶ cells (mean ± SEM), whereas monocytes released only 16 ± 1 and 18 ± 8 pmol per 10⁶ cells of LTB₄ and 5-HETE, respectively. After adding arachidonic acid, macrophages released a maximum of 52 ± 21 pmol of LTB₄ and 223 ± 66 pmol of 5-HETE, whereas monocytes released no detectable products. The results suggest that mononuclear phagocyte maturation in the lung may be accompanied by an enhanced ability to generate 5-lipoxygenase products.