0 7 Hypoxic hypoxic JJ 8 17 induction induction NN 18 20 of of IN 21 34 interleukin-8 interleukin-8 NN 35 39 gene gene NN 40 50 expression expression NN 51 53 in in IN 54 59 human human JJ 60 71 endothelial endothelial JJ 72 77 cells cell NNS 77 78 . . . 80 87 Because because IN 88 106 leukocyte-mediated leukocyte-mediated JJ 107 113 tissue tissue NN 114 120 damage damage NN 121 123 is be VBZ 124 126 an an DT 127 136 important important JJ 137 146 component component NN 147 149 of of IN 150 153 the the DT 154 164 pathologic pathologic JJ 165 172 picture picture NN 173 175 in in IN 176 196 ischemia/reperfusion ischemia/reperfusion NN 196 197 , , , 198 200 we we PRP 201 205 have have VBP 206 212 sought seek VBN 213 223 mechanisms mechanism NNS 224 226 by by IN 227 232 which which WDT 233 237 PMNs pmn NNS 238 241 are be VBP 242 250 directed direct VBN 251 255 into into IN 256 263 hypoxic hypoxic JJ 264 270 tissue tissue NN 270 271 . . . 272 282 Incubation incubation NN 283 285 of of IN 286 291 human human JJ 292 303 endothelial endothelial JJ 304 309 cells cell NNS 310 311 ( ( ( 311 314 ECs EC NNP 314 315 ) ) ) 316 318 in in IN 319 326 hypoxia hypoxia NN 326 327 , , , 328 331 PO2 PO2 NNP 332 345 approximately approximately RB 346 351 14-18 14-18 CD 352 356 Torr Torr NNP 356 357 , , , 358 361 led lead VBD 362 364 to to TO 365 379 time-dependent time-dependent JJ 380 387 release release NN 388 390 of of IN 391 395 IL-8 il-8 NN 396 403 antigen antigen NN 404 408 into into IN 409 412 the the DT 413 424 conditioned condition VBN 425 431 medium medium NN 431 432 ; ; : 433 437 this this DT 438 441 was be VBD 442 453 accompanied accompany VBN 454 456 by by IN 457 466 increased increase VBN 467 478 chemotactic chemotactic JJ 479 487 activity activity NN 488 491 for for IN 492 496 PMNs PMN NNP 496 497 , , , 498 505 blocked block VBN 506 508 by by IN 509 517 antibody antibody NN 518 520 to to TO 521 525 IL-8 il-8 NN 525 526 . . . 527 537 Production production NN 538 540 of of IN 541 545 IL-8 il-8 NN 546 548 by by IN 549 556 hypoxic hypoxic JJ 557 560 ECs ec NNS 561 569 occurred occur VBD 570 583 concomitantly concomitantly RB 584 588 with with IN 589 593 both both DT 594 603 increased increase VBN 604 610 levels level NNS 611 613 of of IN 614 618 IL-8 IL-8 NNP 619 623 mRNA mRNA NNP 623 624 , , , 625 630 based base VBN 631 633 on on IN 634 644 polymerase polymerase NN 645 650 chain chain NN 651 659 reaction reaction NN 660 668 analysis analysis NN 668 669 , , , 670 673 and and CC 674 683 increased increase VBD 684 688 IL-8 il-8 NN 689 702 transcription transcription NN 702 703 , , , 704 709 based base VBN 710 712 on on IN 713 720 nuclear nuclear JJ 721 727 run-on run-on JJ 728 734 assays assay NNS 734 735 . . . 736 744 Northern northern JJ 745 753 analysis analysis NN 754 756 of of IN 757 761 mRNA mrna NN 762 766 from from IN 767 774 hypoxic hypoxic JJ 775 778 ECs ec NNS 779 783 also also RB 784 796 demonstrated demonstrate VBD 797 806 increased increase VBN 807 813 levels level NNS 814 816 of of IN 817 821 mRNA mrna NN 822 825 for for IN 826 836 macrophage macrophage NN 837 848 chemotactic chemotactic JJ 849 858 protein-1 protein-1 NN 858 859 , , , 860 867 another another DT 868 874 member member NN 875 877 of of IN 878 881 the the DT 882 891 chemokine chemokine NN 892 903 superfamily superfamily NN 904 906 of of IN 907 922 proinflammatory proinflammatory JJ 923 932 cytokines cytokine NNS 932 933 . . . 934 938 IL-8 il-8 NN 939 943 gene gene NN 944 953 induction induction NN 954 957 was be VBD 958 968 associated associate VBN 969 973 with with IN 974 977 the the DT 978 986 presence presence NN 987 989 of of IN 990 999 increased increase VBN 1000 1007 binding binding NN 1008 1016 activity activity NN 1017 1019 in in IN 1020 1027 nuclear nuclear JJ 1028 1036 extracts extract NNS 1037 1041 from from IN 1042 1049 hypoxic hypoxic JJ 1050 1053 ECs ec NNS 1054 1057 for for IN 1058 1061 the the DT 1062 1067 NF-kB NF-kB NNP 1068 1072 site site NN 1072 1073 . . . 1074 1081 Studies study NNS 1082 1086 with with IN 1087 1092 human human JJ 1093 1102 umbilical umbilical JJ 1103 1107 vein vein NN 1108 1116 segments segment NNS 1117 1124 exposed expose VBN 1125 1127 to to TO 1128 1135 hypoxia hypoxia NN 1136 1140 also also RB 1141 1153 demonstrated demonstrate VBD 1154 1163 increased increase VBN 1164 1175 elaboration elaboration NN 1176 1178 of of IN 1179 1183 IL-8 il-8 NN 1184 1191 antigen antigen NN 1192 1200 compared compare VBN 1201 1205 with with IN 1206 1214 normoxic normoxic JJ 1215 1223 controls control NNS 1223 1224 . . . 1225 1227 In in IN 1228 1232 mice mouse NNS 1233 1240 exposed expose VBN 1241 1243 to to TO 1244 1251 hypoxia hypoxia NN 1252 1253 ( ( ( 1253 1256 PO2 PO2 NNP 1257 1270 approximately approximately RB 1271 1276 30-40 30-40 CD 1277 1281 Torr Torr NNP 1281 1282 ) ) ) 1282 1283 , , , 1284 1289 there there EX 1290 1293 was be VBD 1294 1303 increased increase VBN 1304 1313 pulmonary pulmonary JJ 1314 1325 leukostasis leukostasis NN 1325 1326 , , , 1327 1329 as as IN 1330 1339 evidenced evidence VBN 1340 1342 by by IN 1343 1352 increased increase VBN 1353 1368 myeloperoxidase myeloperoxidase NN 1369 1377 activity activity NN 1378 1380 in in IN 1381 1387 tissue tissue NN 1388 1399 homogenates homogenate NNS 1399 1400 . . . 1401 1403 In in IN 1404 1412 parallel parallel NN 1412 1413 , , , 1414 1423 increased increase VBN 1424 1430 levels level NNS 1431 1433 of of IN 1434 1445 transcripts transcript NNS 1446 1449 for for IN 1450 1455 IP-10 IP-10 NNP 1455 1456 , , , 1457 1458 a a DT 1459 1465 murine murine JJ 1466 1475 homologue homologue NN 1476 1478 in in IN 1479 1482 the the DT 1483 1492 chemokine chemokine NN 1493 1499 family family NN 1500 1507 related related JJ 1508 1510 to to TO 1511 1515 IL-8 il-8 NN 1515 1516 , , , 1517 1521 were be VBD 1522 1530 observed observe VBN 1531 1533 in in IN 1534 1541 hypoxic hypoxic JJ 1542 1546 lung lung NN 1547 1553 tissue tissue NN 1553 1554 . . . 1555 1560 Taken take VBN 1561 1569 together together RB 1569 1570 , , , 1571 1576 these these DT 1577 1581 data datum NNS 1582 1589 suggest suggest VBP 1590 1594 that that IN 1595 1602 hypoxia hypoxia NN 1603 1614 constitutes constitute VBZ 1615 1616 a a DT 1617 1625 stimulus stimulus NN 1626 1629 for for IN 1630 1639 leukocyte leukocyte NN 1640 1650 chemotaxis chemotaxis NN 1651 1654 and and CC 1655 1661 tissue tissue NN 1662 1673 leukostasis leukostasis NN 1673 1674 . . .