Activation of Leukotriene Synthesis in Human Neutrophils by Exogenous Arachidonic Acid: Inhibition by Adenosine A2aReceptor Agonists and Crucial Role of Autocrine Activation by Leukotriene B4

摘要: We report here that the apparent inability of isolated human polymorphonuclear leukocytes (PMNs) to efficiently transform arachidonic acid (AA) is consequence A(2a) receptor engagement by endogenous adenosine accumulating in incubation media. Indeed, when eliminated from PMN suspensions addition deaminase, or cells are incubated with antagonists, important quantities (40-80 pmol/10(6) cells) 5-lipoxygenase products synthesized 1 5 microM exogenous AA. The selective agonist CGS21680 was a very potent inhibitor AA-induced leukotriene (LT) synthesis, showing an IC(50) approximately nM. mechanism stimulation LT synthesis observed absence extracellular investigated. In deaminase-treated PMN, AA induced Ca(2+) mobilization and translocation nuclear structures. A time lag 20 60 s (variable between preparations) consistently elevation intracellular concentration (and synthesis), indicating itself did not trigger PMN. This mobilization, as well corresponding blocked MK0591, LTB(4) antagonists CP105696 LY223982, LTA(4) hydrolase SC57461A. These data demonstrate highly effective activator acts through requires autocrine stimulatory loop LTB(4).