%PDF-1.3 % 1 0 obj << /Type /Pages /Count 10 /Kids [ 3 0 R 4 0 R 5 0 R 6 0 R 7 0 R 8 0 R 9 0 R 10 0 R 11 0 R 12 0 R ] >> endobj 2 0 obj << /Producer (PyPDF2) /Title (The\040CXC\040Chemokine\040Receptor\0402\054\040CXCR2\054\040Is\040the\040Putative\040Receptor\040for\040ELR\053\040CXC\040Chemokine\055Induced\040Angiogenic\040Activity) /Author (Christina\040L\056\040Addison\054\040Thomas\040O\056\040Daniel\054\040Marie\040D\056\040Burdick\054\040Hua\040Liu\054\040Jan\040E\056\040Ehlert\054\040Ying\040Ying\040Xue\054\040Linda\040Buechi\054\040Alfred\040Walz\054\040Ann\040Richmond\054\040Robert\040M\056\040Strieter) /Subject (We\040have\040previously\040shown\040that\040members\040of\040the\040ELR\050\053\051\040CXC\040chemokine\040family\054\040including\040IL\0558\073\040growth\055related\040oncogenes\040alpha\054\040beta\054\040and\040gamma\073\040granulocyte\040chemotactic\040protein\0402\073\040and\040epithelial\040neutrophil\055activating\040protein\05578\054\040can\040mediate\040angiogenesis\040in\040the\040absence\040of\040preceding\040inflammation\056\040To\040date\054\040the\040receptor\040on\040endothelial\040cells\040responsible\040for\040chemotaxis\040and\040neovascularization\040mediated\040by\040these\040ELR\050\053\051\040CXC\040chemokines\040has\040not\040been\040determined\056\040Because\040all\040ELR\050\053\051\040CXC\040chemokines\040bind\040to\040CXC\040chemokine\040receptor\0402\040\050CXCR2\051\054\040we\040hypothesized\040that\040CXCR2\040is\040the\040putative\040receptor\040for\040ELR\050\053\051\040CXC\040chemokine\055mediated\040angiogenesis\056\040To\040test\040this\040postulate\054\040we\040first\040determined\040whether\040cultured\040human\040microvascular\040endothelial\040cells\040expressed\040CXCR2\056\040CXCR2\040was\040detected\040in\040human\040microvascular\040endothelial\040cells\040at\040the\040protein\040level\040by\040both\040Western\040blot\040analysis\040and\040immunohistochemistry\040using\040polyclonal\040Abs\040specific\040for\040human\040CXCR2\056\040To\040determine\040whether\040CXCR2\040played\040a\040functional\040role\040in\040angiogenesis\054\040we\040determined\040whether\040this\040receptor\040was\040involved\040in\040endothelial\040cell\040chemotaxis\056\040We\040found\040that\040microvascular\040endothelial\040cell\040chemotaxis\040in\040response\040to\040ELR\050\053\051\040CXC\040chemokines\040was\040inhibited\040by\040anti\055CXCR2\040Abs\056\040In\040addition\054\040endothelial\040cell\040chemotaxis\040in\040response\040to\040ELR\050\053\051\040CXC\040chemokines\040was\040sensitive\040to\040pertussis\040toxin\054\040suggesting\040a\040role\040for\040G\040protein\055linked\040receptor\040mechanisms\040in\040this\040biological\040response\056\040The\040importance\040of\040CXCR2\040in\040mediating\040ELR\050\053\051\040CXC\040chemokine\055induced\040angiogenesis\040in\040vivo\040was\040also\040demonstrated\040by\040the\040lack\040of\040angiogenic\040activity\040induced\040by\040ELR\050\053\051\040CXC\040chemokines\040in\040the\040presence\040of\040neutralizing\040Abs\040to\040CXCR2\040in\040the\040rat\040corneal\040micropocket\040assay\054\040or\040in\040the\040corneas\040of\040CXCR2\050\055\057\055\051\040mice\056\040We\040thus\040conclude\040that\040CXCR2\040is\040the\040receptor\040responsible\040for\040ELR\050\053\051\040CXC\040chemokine\055mediated\040angiogenesis\056) 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