RAPID IMPORT OF CYTOSOLIC 5-LIPOXYGENASE INTO THE NUCLEUS OF NEUTROPHILS AFTER IN-VIVO RECRUITMENT AND IN-VITRO ADHERENCE

5-Lipoxygenase catalyzes the synthesis of leukotrienes from arachidoni c acid, The subcellular distribution of 5-lipoxygenase is known to be cell type dependent and is cytosolic in blood neutrophils. In this stu dy, we asked whether neutrophil recruitment into sites of inflammation can alter the subcellular compartmentation of 5-lipoxygenase. In peri pheral blood neutrophils from rats, 5-lipoxygenase was exclusively cyt osolic, as expected, However, in glycogen-elicited peritoneal neutroph ils, abundant soluble 5-lipoxygenase was in the nucleus, Upon activati on with calcium ionophore A23187, intranuclear 5-lipoxygenase transloc ated to the nuclear envelope, Elicited neutrophils required a greater concentration of A23187 for activation than did blood neutrophils (hal f-maximal response, 160 versus 52 nM, respectively) but generated grea ter amounts of leukotriene B-4 upon maximal stimulation (26.6 versus 7 .68 ng/10(6) cells, respectively), Intranuclear 5-lipoxygenase was als o evident in human blood neutrophils after adherence to a variety of s urfaces, suggesting that adherence alone is sufficient to drive 5-lipo xygenase redistribution, These results demonstrate a physiologically r elevant circumstance in which the subcellular distribution of 5-lipoxy genase can be rapidly altered in resting cells, independent of 5-lipox ygenase activation, Nuclear import of 5-lipoxygenase may be a universa l accompaniment of neutrophil recruitment into sites of inflammation, and this may be associated with alterations in enzymatic function.