期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 285, 期 12, 页码 9137-9146出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M109.002774
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资金
- Danish Medical Research Council
- Foundation of A. P. Moller and Chastine McKinney Moller
- Foundation of Arvid Nilsson
- Augustinus Foundation
- Beckett-Foundation
- Foundation of Bent Bogh and Wife
- Foundation of Carl and Ellen Hertz
- Foundation of Christian Larsen and Ellen Larsen
- Foundation of Frode V. Nyegaard and Wife
- Foundation of E. Danielsen and Wife
- Foundation of Einar Hansen and Wife
- Foundation of Michael Hermann Nielsen
- Foundation of Else and Mogens Wedell-Wedellsborg
- Foundation of Karl G Andersen
- Harboe-Foundation
- Foundation of Holger Hjortenberg and Wife
- Illum Foundation
- Foundation of Johan Boserup and Lise Boserup
- Foundation of Niels Hansen and Wife
- Foundation of Werner Richter and Wife
- Foundation of Ove William Buhl Olesen and Wife
- Foundation of Meta and HAkon Bagger
- Foundation of Jakob Madsen and Wife
Large DNA viruses, such as herpesvirus and poxvirus, encode proteins that target and exploit the chemokine system of their host. UL146 and UL147 in the cytomegalovirus (CMV) genome encode the two CXC chemokines vCXCL1 and vCXCL2. In this study, vCXCL1 was probed against a panel of the 18 classified human chemokine receptors. In calcium mobilization assays vCXCL1 acted as an agonist on both CXCR1 and CXCR2 but did not activate or block any of the other 16 chemokine receptors. vCXCL1 was characterized and compared with CXCL1/GRO alpha, CXCL2/GRO beta, CXCL3/GRO gamma, CXCL5/ENA-78, CXCL6/GCP2, CXCL7/NAP-2 and CXCL8/IL-8 in competition binding, calcium mobilization, inositol triphosphate turnover, and chemotaxis assays using CXCR1- and CXCR2-expressing Chinese hamster ovary, 300.19, COS7, and L1.2 cells. The affinities of vCXCL1 for the CXCR1 and CXCR2 receptors were 44 and 5.6 nM, respectively, as determined in competition binding against radioactively labeled CXCL8. In calcium mobilization, phosphatidylinositol turnover, and chemotaxis assays, vCXCL1 acted as a highly efficacious activator of both receptors, with a rather low potency for the CXCR1 receptor but comparable with CXCL5 and CXCL7. It is suggested that CMV uses the UL146 gene product expressed in infected endothelial cells to attract neutrophils by activating their CXCR1 and CXCR2 receptors, whereby neutrophils can act as carriers of the virus to uninfected endothelial cells. In that way a lasting pool of CMV-infected endothelial cells could be maintained.
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