CARRIER-MEDIATED TRANSPORT OF LIPOXIN A(4) IN HUMAN NEUTROPHILS

Lipoxins and other eicosanoids display potent and selective biological effects on leukocytes. In this study, we utilized radiolabeled lipoxi n A(4) ([H-3]LXA(4)) to investigate whether carrier-mediated transport of LXA(4) might occur in human neutrophils. At a concentration of 5 n M, uptake of [H-3]LXA(4), above that due to specific binding to recept ors, amounted to similar to 0.6 fmol.10(6) cells(-1) min(-1). This inf lux was sensitive to a number of anionic inhibitors, including 3,5-dii odosalicylic acid (K-0.5 12 mu M), pentachlorophenol (K-0.5 25 mu M), alpha-cyano-beta-(1-phenylindol-3-yl) acrylic acid, and the organomerc urial agents mersalyl (K-0.5 110 mu M) and p-hydroxy-mercuribenzoate. Influx, which was Na+ and membrane voltage independent, exhibited a st riking dependence on pH (negative log of dissociation 5.9), results co mpatible with an H+ + LXA(4) anion cotransport system. The LXA(4) carr ier did not appear to interact with arachidonic acid, prostaglandin E( 2), 15(S)-hydroxy-(5Z,8Z,11Z,13E)-eicosatetraenoic acid, or the leukot rienes B-4, C-4, and D-4. Moreover, transport activity was not observe d in human erythrocytes, lymphocytes, or platelets, but it was inducib le in HL-60 cells on differentiation by exposure to retinoic acid. The se findings represent the identification and initial characterization of a novel carrier-mediated pathway in human neutrophils that facilita tes transport of LXA(4) into cells.