A23187 stimulates translocation of 5-lipoxygenase from cytosol to membrane in human alveolar macrophages.
Human alveolar macrophages stimulated with the calcium ionophore A23187 selectively release large amounts of leukotriene B4 (LTB4) and (+/-)-5-hydroxy-(6E, 8Z-11Z, 14Z)-eicosatetraenoic acid. To determine whether LTB4 release by human alveolar macrophages following A23187 stimulation required the de novo production of 5-lipoxygenase, alveolar macrophages were stimulated under conditions that would preclude a role for new enzyme production. We found that A23187-stimulated alveolar macrophages release LTB4 within 10 min following stimulation, that LTB4 release is not inhibited by protein synthesis inhibitors, and that release of LTB4 does not correlate with the de novo synthesis of the first committed enzyme, 5-lipoxygenase. In contrast, LTB4 release correlated with the translocation of 5-lipoxygenase from the cytosol to the membrane fraction of the cells following A23187 stimulation and was inhibited by MK-886. These findings show that A23187 stimulation of alveolar macrophages results in translocation of a preexistent 5-lipoxygenase from the cytosol to the membrane fraction of the cell and that this translocation of 5-lipoxygenase is associated with release of LTB4 from the cells.
Pueringer
R J
RJ
Department of Internal Medicine, Department of Veterans Affairs Medical Center, Iowa City, Iowa 52242.
Bahns
C C
CC
Monick
M M
MM
Hunninghake
G W
GW
D001094:Arachidonate 5-Lipoxygenase / Q000235:genetics* / Q000378:metabolism; D000001:Calcimycin / Q000494:pharmacology*; D002462:Cell Membrane / Q000201:enzymology; D003600:Cytosol / Q000201:enzymology*; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D020024:Leukotriene Antagonists; D007975:Leukotriene B4 / Q000096:biosynthesis; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D016676:Macrophages, Alveolar / Q000201:enzymology*; D014178:Translocation, Genetic / Q000187:drug effects*; D002722:Chlorobenzenes
D001094:Arachidonate 5-Lipoxygenase; D000001:Calcimycin; D007211:Indoles; D020024:Leukotriene Antagonists; D007975:Leukotriene B4; D016859:Lipoxygenase Inhibitors; C060893:MK-886; D002722:Chlorobenzenes