HUMAN MONOCYTES LOSE 5-LIPOXYGENASE AND FLAP AS THEY MATURE INTO MONOCYTE-DERIVED MACROPHAGES IN-VITRO

Previous studies in mononuclear phagocytes have shown that macrophages have substantially greater 5-lipoxygenase activity than monocytes and that this is associated with greater amounts of 5-lipoxygenase and it s activating protein (FLAP). The aim of this study was to examine the effect of mononuclear phagocyte maturation in vitro on 5-lipoxygenase expression. At baseline, monocytes had significant 5-lipoxygenase acti vity, but then lost all detectable 5-lipoxygenase activity over 7 days . Immunoblot and Northern blot analysis revealed that immunoreactive p rotein and mRNA for both 5-lipoxygenase and FLAP were significantly de creased over time. These studies demonstrate that in vitro differentia tion of monocytes into a macrophage phenotype is not accompanied by th e enhanced expression of 5-lipoxygenase and FLAP seen in macrophages d erived from in vivo sources. In fact, baseline expression of 5-lipoxyg enase and FLAP by monocytes is lost in vitro. These studies have clear implications for the use of cultured monocytes as a model of macropha ges, and they also further our understanding of the regulation of the 5-lipoxygenase pathway.