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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
2003-2-17
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pubmed:abstractText |
The mechanism by which inflammatory cells are recruited to pig islet tissue (proislet) xenografts was investigated by examining the intragraft mRNA expression of murine alpha- and beta-chemokines in CBA/H mice from days 3 to 10 post-transplant. Xenograft rejection was associated with early intragraft transcript expression for monocyte chemotactic protein-1 (MCP-1) (3 to 5 days), IP-10 (3 to 4 days) and macrophage inflammatory protein-1alpha (MIP-1alpha) (3 to 5 days) and subsequent expression of eotaxin (days 4 to 10), MIP-1beta (days 4 and 5) and regulated on activation, normal T cell expressed and secreted (RANTES) (days 4 to 6) mRNA. This pattern was consistent with the early recruitment of macrophages (MCP-1, MIP-1alpha), the influx of CD4 T cells (MCP-1, MIP-1alpha, MIP-1beta, IP-10 and RANTES) and the characteristic infiltrate of eosinophils (eotaxin and RANTES) associated with islet xenograft rejection. Inhibition of beta-chemokine signaling in CCR2-/- mice (which lack the major co-receptor for MCP-1) resulted in retarded macrophage and CD4 T cell recruitment, enhanced eosinophil influx and a minor delay in rejection, compared with wildtype mice; there was little effect on leukocyte infiltration in xenografts harvested from CCR5-/- mice (lacking the co-receptor for MIP-1alpha, MIP-1beta and RANTES). The impeded migration of leukocytes into xenografts in CCR2-/- hosts was associated with delayed intragraft expression of MCP-1 and RANTES mRNA; absence of MCP-1/CCR2-mediated signaling led to enhanced intragraft expression of MCP-1, MIP-1alpha and MIP-1beta mRNA. These findings suggest that MCP-1 plays an important role in regulating macrophage and CD4 T cell infiltration to xenograft sites via the CCR2 signaling pathway. Additional treatment of xenografted CCR2-/- transplant recipients with anti-interleukin-(IL)-4 and anti-IL-5 mAbs further delayed xenograft rejection demonstrating the potential for combined antirejection strategies in facilitating pig islet xenotransplantation.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Monoclonal,
http://linkedlifedata.com/resource/pubmed/chemical/Ccr2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Chemokine CCL2,
http://linkedlifedata.com/resource/pubmed/chemical/Chemokine CCL3,
http://linkedlifedata.com/resource/pubmed/chemical/Chemokine CCL4,
http://linkedlifedata.com/resource/pubmed/chemical/Chemokine CCL5,
http://linkedlifedata.com/resource/pubmed/chemical/Chemokine CXCL10,
http://linkedlifedata.com/resource/pubmed/chemical/Chemokines,
http://linkedlifedata.com/resource/pubmed/chemical/Chemokines, CXC,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-4,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-5,
http://linkedlifedata.com/resource/pubmed/chemical/Macrophage Inflammatory Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, CCR2,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, CCR5,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Chemokine
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0908-665X
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
10
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
164-77
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:12588649-Animals,
pubmed-meshheading:12588649-Antibodies, Monoclonal,
pubmed-meshheading:12588649-CD4-Positive T-Lymphocytes,
pubmed-meshheading:12588649-Chemokine CCL2,
pubmed-meshheading:12588649-Chemokine CCL3,
pubmed-meshheading:12588649-Chemokine CCL4,
pubmed-meshheading:12588649-Chemokine CCL5,
pubmed-meshheading:12588649-Chemokine CXCL10,
pubmed-meshheading:12588649-Chemokines,
pubmed-meshheading:12588649-Chemokines, CXC,
pubmed-meshheading:12588649-Gene Expression,
pubmed-meshheading:12588649-Graft Rejection,
pubmed-meshheading:12588649-Graft Survival,
pubmed-meshheading:12588649-Immunohistochemistry,
pubmed-meshheading:12588649-Interleukin-4,
pubmed-meshheading:12588649-Interleukin-5,
pubmed-meshheading:12588649-Islets of Langerhans Transplantation,
pubmed-meshheading:12588649-Macrophage Inflammatory Proteins,
pubmed-meshheading:12588649-Male,
pubmed-meshheading:12588649-Mice,
pubmed-meshheading:12588649-Mice, Inbred C57BL,
pubmed-meshheading:12588649-Mice, Inbred CBA,
pubmed-meshheading:12588649-Mice, Knockout,
pubmed-meshheading:12588649-RNA, Messenger,
pubmed-meshheading:12588649-Receptors, CCR2,
pubmed-meshheading:12588649-Receptors, CCR5,
pubmed-meshheading:12588649-Receptors, Chemokine,
pubmed-meshheading:12588649-Swine,
pubmed-meshheading:12588649-Transplantation, Heterologous
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pubmed:year |
2003
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pubmed:articleTitle |
The role of chemokines and their receptors in the rejection of pig islet tissue xenografts.
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pubmed:affiliation |
Division of Molecular Medicine, The John Curtin School of Medical Research, The Australian National University, Canberra, ACT, Australia.
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pubmed:publicationType |
Journal Article
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