Biphasic effect of cadmium ions on the secretion of leukotriene B4 in rabbit alveolar macrophages.
One major role of alveolar macrophages is the production of eicosanoids, which modulate immune and inflammatory processes in the lung. In this study, the effects were investigated of cadmium ions on the secretion of leukotriene (LT)B4 and prostaglandin (PG)E2, predominant products of lipoxygenase and cyclooxygenase, respectively. Cd2+ had an inhibitory effect on the secretion of LTB4 and PGE2 in response to A23187 stimulation at concentrations > 3 x 10(-5)M. This effect can be explained by the inhibition of arachidonic acid (20:4) liberation from membrane phospholipids by Cd2+, because Cd2+ inhibits both [3H] arachidonic acid (20:4) liberation from [3H]20:4-prelabeled macrophages and the cytosolic phospholipase A2 activity. At concentrations < 3 x 10(-5)M, Cd2+ had no effect on PGE2 secretion but showed an augmentation of LTB4 secretion. In vitro study using macrophage lysate showed enhanced LTB4 synthesis from arachidonic acid by Cd2+, which could be responsible for the augmentation of LTB4 secretion in cells. These results indicate that Cd2+ may increase inflammation by increasing LTB4 production in lung.
Faculty of Pharmaceutical Sciences, Teikyo University, Kanagawa, Japan.
N
N
Kudo
Y
Y
Nakagawa
K
K
Waku
D000704:Analysis of Variance; D000818:Animals; D000900:Anti-Bacterial Agents / Q000633:toxicity; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism; D016718:Arachidonic Acid / Q000037:antagonists & inhibitors / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D019256:Cadmium Chloride / Q000378:metabolism / Q000633:toxicity*; D000001:Calcimycin / Q000633:toxicity; D002118:Calcium / Q000494:pharmacology; D003600:Cytosol / Q000187:drug effects / Q000201:enzymology; D015232:Dinoprostone / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D007975:Leukotriene B4 / Q000378:metabolism*; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000378:metabolism; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D011817:Rabbits; D011863:Radioimmunoassay
D000900:Anti-Bacterial Agents; D007975:Leukotriene B4; D016718:Arachidonic Acid; D000001:Calcimycin; D001094:Arachidonate 5-Lipoxygenase; D010741:Phospholipases A; D054467:Phospholipases A2; D019256:Cadmium Chloride; D015232:Dinoprostone; D002118:Calcium