Donor-Derived Ip-10 Initiates Development of Acute Allograft Rejection
| Autor: | Wayne W. Hancock, Kerrie L. Faia, Nida Shemmeri, Wei Gao, Vilmos Csizmadia, Andrew D. Luster |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2001 |
| Předmět: |
Graft Rejection
Chemokine Receptors CXCR3 endothelium medicine.medical_treatment Immunology Mice Inbred Strains Biology IP-10 CXCR3 Interferon-gamma Mice medicine Immunology and Allergy CXCL10 Animals Transplantation Homologous CXCL11 Mice Knockout Mice Inbred BALB C chemokine Graft Survival Brief Definitive Report medicine.disease Transplant rejection Monokine Chemokine CXCL10 Mice Inbred C57BL Transplantation Isogeneic Cytokine Acute Disease biology.protein CXCL9 Heart Transplantation Receptors Chemokine rejection Chemokines Chemokines CXC transplantation |
| Zdroj: | The Journal of Experimental Medicine |
| ISSN: | 1540-9538 0022-1007 |
| Popis: | An allograft is often considered an immunologically inert playing field on which host leukocytes assemble and wreak havoc. However, we demonstrate that graft-specific physiologic responses to early injury initiate and promulgate destruction of vascularized grafts. Serial analysis of allografts showed that intragraft expression of the three chemokine ligands for the CXC chemo-kine receptor CXCR3 was induced in the order of interferon (IFN)-gamma-inducible protein of 10 kD (IP-10, or CXCL10), IFN-inducible T cell alpha-chemoattractant (I-TAC; CXCL11), and then monokine induced by IFN-gamma (Mig, CXCL9). Initial IP-10 production was localized to endothelial cells, and only IP-10 was induced by isografting. Anti-IP-10 monoclonal antibodies prolonged allograft survival, but surprisingly, IP-10-deficient (IP-10(-/-)) mice acutely rejected allografts. However, though allografts from IP-10(+/+) mice were rejected by day 7, hearts from IP-10(-/-) mice survived long term. Compared with IP-10(+/+) donors, use of IP-10(-/-) donors reduced intragraft expression of cytokines, chemokines and their receptors, and associated leukocyte infiltration and graft injury. Hence, tissue-specific generation of a single chemokine in response to initial ischemia/reperfusion can initiate progressive graft infiltration and amplification of multiple effector pathways, and targeting of this proximal chemokine can prevent acute rejection. These data emphasize the pivotal role of donor-derived IP-10 in initiating alloresponses, with implications for tissue engineering to decrease immunogenicity, and demonstrate that chemokine redundancy may not be operative in vivo. |
| Databáze: | OpenAIRE |
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