0 6 Cobalt Cobalt NNP 7 23 chloride-induced chloride-induced JJ 24 33 signaling signaling NN 34 36 in in IN 37 48 endothelium endothelium NN 49 56 leading lead VBG 57 59 to to TO 60 63 the the DT 64 73 augmented augmented JJ 74 83 adherence adherence NN 84 86 of of IN 87 93 sickle sickle JJ 94 97 red red JJ 98 103 blood blood NN 104 109 cells cell NNS 110 113 and and CC 114 130 transendothelial transendothelial JJ 131 140 migration migration NN 141 143 of of IN 144 157 monocyte-like monocyte-like JJ 158 163 HL-60 hl-60 NN 164 169 cells cell NNS 170 172 is be VBZ 173 180 blocked block VBN 181 183 by by IN 184 196 PAF-receptor PAF-receptor NNP 197 207 antagonist antagonist NN 207 208 . . . 210 212 In in IN 213 221 response response NN 222 224 to to TO 225 232 hypoxia hypoxia NN 232 233 , , , 234 240 sickle sickle JJ 241 244 red red JJ 245 250 blood blood NN 251 256 cells cell NNS 257 258 ( ( ( 258 260 SS SS NNP 261 264 RBC RBC NNP 264 265 ) ) ) 266 269 and and CC 270 280 leukocytes leukocyte NNS 281 288 exhibit exhibit VBP 289 298 increased increase VBN 299 308 adherence adherence NN 309 311 to to TO 312 315 the the DT 316 324 vascular vascular JJ 325 336 endothelium endothelium NN 336 337 , , , 338 343 while while IN 344 354 diapedesis diapedesis NN 355 357 of of IN 358 368 leukocytes leukocyte NNS 369 376 through through IN 377 380 the the DT 381 386 blood blood NN 387 393 vessel vessel NN 394 403 increases increase NNS 403 404 . . . 405 412 However however RB 412 413 , , , 414 417 the the DT 418 426 cellular cellular JJ 427 436 signaling signaling NN 437 447 pathway(s) pathway(s) NN 448 454 caused cause VBN 455 457 by by IN 458 465 hypoxia hypoxia NN 466 468 is be VBZ 469 475 poorly poorly RB 476 486 understood understand VBN 486 487 . . . 488 490 We we PRP 491 499 utilized utilize VBD 500 505 CoCl2 cocl2 NN 506 508 as as IN 509 510 a a DT 511 518 mimetic mimetic JJ 519 527 molecule molecule NN 528 531 for for IN 532 539 hypoxia hypoxia NN 540 542 to to TO 543 548 study study VB 549 557 cellular cellular JJ 558 567 signaling signaling NN 568 576 pathways pathway NNS 576 577 . . . 578 580 We we PRP 581 586 found find VBD 587 591 that that IN 592 594 in in IN 595 600 human human JJ 601 610 umbilical umbilical JJ 611 615 vein vein NN 616 627 endothelial endothelial JJ 628 633 cells cell NNS 634 635 ( ( ( 635 640 HUVEC HUVEC NNP 640 641 ) ) ) 641 642 , , , 643 648 CoCl2 cocl2 NN 649 651 at at IN 652 653 2 2 CD 654 656 mM mm NN 657 670 concentration concentration NN 671 678 induced induce VBD 679 682 the the DT 683 690 surface surface NN 691 701 expression expression NN 702 704 of of IN 705 706 a a DT 707 713 subset subset NN 714 716 of of IN 717 721 CAMs CAM NNP 722 723 ( ( ( 723 729 VCAM-1 VCAM-1 NNP 729 730 ) ) ) 731 734 and and CC 735 745 activation activation NN 746 748 of of IN 749 762 transcription transcription NN 763 769 factor factor NN 770 779 NF-kappaB nf-kappab NN 780 782 in in IN 783 786 the the DT 787 794 nuclear nuclear JJ 795 803 extracts extract NNS 804 806 of of IN 807 812 HUVEC HUVEC NNP 812 813 . . . 814 825 Furthermore furthermore RB 825 826 , , , 827 832 CoCl2 CoCl2 NNP 833 837 also also RB 838 844 caused cause VBD 845 859 time-dependent time-dependent JJ 860 868 tyrosine tyrosine NN 869 884 phosphorylation phosphorylation NN 885 887 of of IN 888 905 mitogen-activated mitogen-activated JJ 906 913 protein protein NN 914 915 ( ( ( 915 918 MAP MAP NNP 918 919 ) ) ) 920 926 kinase kinase NNP 927 934 isoform isoform NN 935 939 ERK2 erk2 NN 940 947 without without IN 948 961 significantly significantly RB 962 971 affecting affect VBG 972 976 ERK1 erk1 NN 976 977 , , , 978 988 indicating indicate VBG 989 993 ERK2 erk2 NN 994 996 is be VBZ 997 1000 the the DT 1001 1010 preferred prefer VBN 1011 1020 substrate substrate NN 1021 1024 for for IN 1025 1033 upstream upstream JJ 1034 1040 kinase kinase NNP 1041 1043 of of IN 1044 1047 the the DT 1048 1052 MAPK MAPK NNP 1053 1060 pathway pathway NN 1060 1061 . . . 1062 1072 Inhibitors inhibitor NNS 1073 1075 of of IN 1076 1079 MAP MAP NNP 1080 1086 kinase kinase NNP 1087 1088 ( ( ( 1088 1095 PD98059 PD98059 NNP 1095 1096 ) ) ) 1097 1099 or or CC 1100 1119 platelet-activating platelet-activating JJ 1120 1126 factor factor NN 1127 1128 ( ( ( 1128 1133 PAF)- paf)- NN 1134 1142 receptor receptor NN 1143 1153 antagonist antagonist NN 1154 1155 ( ( ( 1155 1161 CV3988 cv3988 NN 1161 1162 ) ) ) 1163 1172 inhibited inhibit VBD 1173 1176 the the DT 1177 1190 CoCl2-induced cocl2-induced JJ 1191 1200 NF-kappaB NF-kappaB NNP 1201 1211 activation activation NN 1212 1215 and and CC 1216 1222 VCAM-1 vcam-1 NN 1223 1233 expression expression NN 1233 1234 . . . 1235 1244 Augmented augmented JJ 1245 1255 expression expression NN 1256 1258 of of IN 1259 1265 VCAM-1 vcam-1 NN 1266 1269 led lead VBD 1270 1272 to to TO 1273 1282 increased increase VBN 1283 1285 SS SS NNP 1286 1289 RBC RBC NNP 1290 1298 adhesion adhesion NN 1298 1299 , , , 1300 1311 inhibitable inhibitable JJ 1312 1314 by by IN 1315 1316 a a DT 1317 1323 VCAM-1 vcam-1 NN 1324 1332 antibody antibody NN 1332 1333 . . . 1334 1346 Additionally additionally RB 1346 1347 , , , 1348 1353 CoCl2 CoCl2 NNP 1354 1360 caused cause VBD 1361 1362 a a DT 1363 1367 two- two- CD 1368 1370 to to TO 1371 1380 threefold threefold JJ 1381 1389 increase increase NN 1390 1392 in in IN 1393 1396 the the DT 1397 1401 rate rate NN 1402 1404 of of IN 1405 1421 transendothelial transendothelial JJ 1422 1431 migration migration NN 1432 1434 of of IN 1435 1448 monocyte-like monocyte-like JJ 1449 1454 HL-60 hl-60 NN 1455 1460 cells cell NNS 1461 1464 and and CC 1465 1466 a a DT 1467 1477 twentyfold twentyfold JJ 1478 1486 increase increase NN 1487 1489 in in IN 1490 1505 phosphorylation phosphorylation NN 1506 1508 of of IN 1509 1517 platelet platelet NN 1518 1529 endothelial endothelial JJ 1530 1534 cell cell NN 1535 1543 adhesion adhesion NN 1544 1553 molecules molecule NNS 1554 1555 ( ( ( 1555 1562 PECAM-1 pecam-1 NN 1562 1563 ) ) ) 1563 1564 . . . 1565 1568 The the DT 1569 1585 transendothelial transendothelial JJ 1586 1595 migration migration NN 1596 1598 of of IN 1599 1608 monocytes monocyte NNS 1609 1612 was be VBD 1613 1622 inhibited inhibit VBN 1623 1625 by by IN 1626 1628 an an DT 1629 1637 antibody antibody NN 1638 1640 to to TO 1641 1648 PECAM-1 pecam-1 NN 1648 1649 . . . 1650 1654 Both both CC 1655 1670 phosphorylation phosphorylation NN 1671 1673 of of IN 1674 1681 PECAM-1 pecam-1 NN 1682 1685 and and CC 1686 1702 transendothelial transendothelial JJ 1703 1712 migration migration NN 1713 1715 of of IN 1716 1725 monocytes monocyte NNS 1726 1728 in in IN 1729 1737 response response NN 1738 1740 to to TO 1741 1746 CoCl2 CoCl2 NNP 1747 1751 were be VBD 1752 1761 inhibited inhibit VBN 1762 1764 by by IN 1765 1772 protein protein NN 1773 1779 kinase kinase NNP 1780 1789 inhibitor inhibitor NN 1790 1791 ( ( ( 1791 1800 GF109203X GF109203X NNP 1800 1801 ) ) ) 1802 1805 and and CC 1806 1815 augmented augment VBN 1816 1818 by by IN 1819 1826 protein protein NN 1827 1838 phosphatase phosphatase NN 1839 1848 inhibitor inhibitor NN 1849 1850 ( ( ( 1850 1859 Calyculin Calyculin NNP 1860 1861 A A NNP 1861 1862 ) ) ) 1862 1863 . . . 1864 1867 Our our PRP$ 1868 1872 data datum NNS 1873 1881 suggests suggest VBZ 1882 1886 that that IN 1887 1900 CoCl2-induced cocl2-induced JJ 1901 1909 cellular cellular JJ 1910 1917 signals signal NNS 1918 1927 directing direct VBG 1928 1937 increased increase VBN 1938 1948 expression expression NN 1949 1951 of of IN 1952 1958 VCAM-1 vcam-1 NN 1959 1961 in in IN 1962 1967 HUVEC HUVEC NNP 1968 1975 involve involve VBP 1976 1986 downstream downstream JJ 1987 1997 activation activation NN 1998 2000 of of IN 2001 2004 MAP MAP NNP 2005 2011 kinase kinase NNP 2012 2015 and and CC 2016 2025 NF-kappaB NF-kappaB NNP 2025 2026 , , , 2027 2032 while while IN 2033 2036 the the DT 2037 2052 phosphorylation phosphorylation NN 2053 2055 of of IN 2056 2063 PECAM-1 pecam-1 NN 2064 2070 occurs occur VBZ 2071 2073 as as IN 2074 2075 a a DT 2076 2082 result result NN 2083 2085 of of IN 2086 2096 activation activation NN 2097 2099 of of IN 2100 2103 PKC PKC NNP 2103 2104 . . . 2105 2107 We we PRP 2108 2116 conclude conclude VBP 2117 2121 that that IN 2122 2134 PAF-receptor PAF-receptor NNP 2135 2145 antagonist antagonist NN 2146 2154 inhibits inhibit VBZ 2155 2158 the the DT 2159 2165 CoCl2- cocl2- NN 2166 2168 or or CC 2169 2184 hypoxia-induced hypoxia-induced JJ 2185 2193 increase increase NN 2194 2196 in in IN 2197 2200 the the DT 2201 2209 adhesion adhesion NN 2210 2212 of of IN 2213 2215 SS SS NNP 2216 2219 RBC RBC NNP 2219 2220 , , , 2221 2228 PECAM-1 pecam-1 NN 2229 2244 phosphorylation phosphorylation NN 2244 2245 , , , 2246 2249 and and CC 2250 2253 the the DT 2254 2265 concomitant concomitant JJ 2266 2282 transendothelial transendothelial JJ 2283 2292 migration migration NN 2293 2295 of of IN 2296 2305 monocytes monocyte NNS 2305 2306 . . .