Rapid import of cytosolic 5-lipoxygenase into the nucleus of neutrophils after in vivo recruitment and in vitro adherence.

Abstract

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.

• Authors: T G Brock, R W McNish, M B Bailie, M Peters-Golden
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 272 Issue 13 Pg. 8276-80 (Mar 28 1997) ISSN: 0021-9258 [Print] United States
• PMID: 9079648 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Leukotriene B4
• Calcimycin
• Glycogen
• Arachidonate 5-Lipoxygenase

Topics

• Animals
• Arachidonate 5-Lipoxygenase (metabolism)
• Calcimycin (pharmacology)
• Cell Adhesion
• Cell Nucleus (enzymology)
• Cytosol (enzymology)
• Enzyme Activation
• Glycogen (metabolism)
• Humans
• Leukotriene B4 (metabolism)
• Neutrophils (enzymology)
• Rats