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 arachidonic acid. The subcellular distribution of 5-lipoxygenase is known to be cell type-dependent and is cytosolic in blood neutrophils. In this study, we asked whether neutrophil recruitment into sites of inflammation can alter the subcellular compartmentation of 5-lipoxygenase. In peripheral blood neutrophils from rats, 5-lipoxygenase was exclusively cytosolic, as expected. However, in glycogen-elicited peritoneal neutrophils, abundant soluble 5-lipoxygenase was in the nucleus. Upon activation with calcium ionophore A23187, intranuclear 5-lipoxygenase translocated to the nuclear envelope. Elicited neutrophils required a greater concentration of A23187 for activation than did blood neutrophils (half-maximal response, 160 versus 52 nM, respectively) but generated greater amounts of leukotriene B4 upon maximal stimulation (26.6 versus 7.68 ng/10(6) cells, respectively). Intranuclear 5-lipoxygenase was also evident in human blood neutrophils after adherence to a variety of surfaces, suggesting that adherence alone is sufficient to drive 5-lipoxygenase redistribution. These results demonstrate a physiologically relevant circumstance in which the subcellular distribution of 5-lipoxygenase can be rapidly altered in resting cells, independent of 5-lipoxygenase activation. Nuclear import of 5-lipoxygenase may be a universal accompaniment of neutrophil recruitment into sites of inflammation, and this may be associated with alterations in enzymatic function.
Brock
T G
TG
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109-0652, USA.
McNish
R W
RW
Bailie
M B
MB
Peters-Golden
M
M
D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism*; D000001:Calcimycin / Q000494:pharmacology; D002448:Cell Adhesion; D002467:Cell Nucleus / Q000201:enzymology; D003600:Cytosol / Q000201:enzymology; D004789:Enzyme Activation; D006003:Glycogen / Q000378:metabolism; D006801:Humans; D007975:Leukotriene B4 / Q000378:metabolism; D009504:Neutrophils / Q000201:enzymology*; D051381:Rats
D007975:Leukotriene B4; D000001:Calcimycin; D006003:Glycogen; D001094:Arachidonate 5-Lipoxygenase