Repeated CXCR4 Blockade by Plerixafor Attenuates Transplant Vasculopathy in Murine Aortic Allografts
Plerixafor, a hematopoietic stem cell mobilization agent, increases the peripheral blood content of effector and regulatory T cells and may have beneficial effects on cardiac allograft vasculopathy. The aim of the current study was to evaluate its effects in a murine aortic allograft model using dif...
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| Veröffentlicht in: | The Journal of immunology (1950) 2024-11, Vol.213 (10), p.1542-1552 |
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| container_title | The Journal of immunology (1950) |
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| creator | Theil, Frank Kuckhahn, Annika Hörning, André Völkl, Simon Knab, Katharina Fritz, Niklas Gräbner, Cindy Ramsperger-Gleixner, Martina Weyand, Michael Heim, Christian |
| description | Plerixafor, a hematopoietic stem cell mobilization agent, increases the peripheral blood content of effector and regulatory T cells and may have beneficial effects on cardiac allograft vasculopathy. The aim of the current study was to evaluate its effects in a murine aortic allograft model using different application procedures. Allogeneic donor aorta grafts (n = 8/group) from C57BL/6 mice(H2b) were abdominally transplanted into CBA mice (H2k). Plerixafor application was performed either continuously for 14 d using abdominally implanted osmotic pumps (1 mg/kg/d) or i.p. with a single dose (1 and 5 mg/kg) on day 0 or pulsed injections of 1 mg/kg on days 0, 7, 14, and 21. Cell distribution was monitored by FACS. Aortic grafts were evaluated for neointima development by Elastica-van-Gieson on day 30. Immunofluorescence and intragraft gene expression analysis were performed. On day 14, significantly fewer hematopoietic stem cells were found in the bone marrow of all plerixafor-treated mice. In the pulsed application group, significantly more hematopoietic stem cells were found in the peripheral blood on day 14 (0.045 ± 0.002%; p |
| doi_str_mv | 10.4049/jimmunol.2300632 |
| format | Article |
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The aim of the current study was to evaluate its effects in a murine aortic allograft model using different application procedures. Allogeneic donor aorta grafts (n = 8/group) from C57BL/6 mice(H2b) were abdominally transplanted into CBA mice (H2k). Plerixafor application was performed either continuously for 14 d using abdominally implanted osmotic pumps (1 mg/kg/d) or i.p. with a single dose (1 and 5 mg/kg) on day 0 or pulsed injections of 1 mg/kg on days 0, 7, 14, and 21. Cell distribution was monitored by FACS. Aortic grafts were evaluated for neointima development by Elastica-van-Gieson on day 30. Immunofluorescence and intragraft gene expression analysis were performed. On day 14, significantly fewer hematopoietic stem cells were found in the bone marrow of all plerixafor-treated mice. In the pulsed application group, significantly more hematopoietic stem cells were found in the peripheral blood on day 14 (0.045 ± 0.002%; p < 0.01 [pulsed]; versus 0.0068 ± 0.002% [control]) and also more regulatory T cells. PCR revealed lower inflammatory cytokines. The luminal occlusion was significantly reduced in the pulsed treated group (33.65 ± 8.84 versus 53.13 ± 12.41) going along with decreased neointimal CD4+ T cell and plasmacytoid dendritic cell infiltration, as well as less smooth muscle cell proliferation. The application of plerixafor attenuates chronic rejection in aortic allografts via immunomodulatory effects. Injection of repeated low-dose plerixafor is the most effective application form in the aortic transplant model.</description><identifier>ISSN: 0022-1767</identifier><identifier>ISSN: 1550-6606</identifier><identifier>EISSN: 1550-6606</identifier><identifier>DOI: 10.4049/jimmunol.2300632</identifier><identifier>PMID: 39382301</identifier><language>eng</language><publisher>United States</publisher><subject>Allografts ; Animals ; Aorta - immunology ; Benzylamines ; Cyclams ; Graft Rejection - immunology ; Graft Rejection - prevention & control ; Hematopoietic Stem Cell Mobilization - methods ; Heterocyclic Compounds - administration & dosage ; Heterocyclic Compounds - pharmacology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Inbred CBA ; Neointima - immunology ; Receptors, CXCR4 - antagonists & inhibitors ; T-Lymphocytes, Regulatory - immunology ; Transplantation, Homologous</subject><ispartof>The Journal of immunology (1950), 2024-11, Vol.213 (10), p.1542-1552</ispartof><rights>Copyright © 2024 by The American Association of Immunologists, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c182t-359994d0c7e41f2054a66fb315ca3d229a941b4c7b62446a15f6254a5280b17c3</cites><orcidid>0009-0001-0533-7214 ; 0009-0002-2940-9160 ; 0009-0001-9533-805X ; 0000-0001-5884-5856 ; 0000-0001-6241-7168</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39382301$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Theil, Frank</creatorcontrib><creatorcontrib>Kuckhahn, Annika</creatorcontrib><creatorcontrib>Hörning, André</creatorcontrib><creatorcontrib>Völkl, Simon</creatorcontrib><creatorcontrib>Knab, Katharina</creatorcontrib><creatorcontrib>Fritz, Niklas</creatorcontrib><creatorcontrib>Gräbner, Cindy</creatorcontrib><creatorcontrib>Ramsperger-Gleixner, Martina</creatorcontrib><creatorcontrib>Weyand, Michael</creatorcontrib><creatorcontrib>Heim, Christian</creatorcontrib><title>Repeated CXCR4 Blockade by Plerixafor Attenuates Transplant Vasculopathy in Murine Aortic Allografts</title><title>The Journal of immunology (1950)</title><addtitle>J Immunol</addtitle><description>Plerixafor, a hematopoietic stem cell mobilization agent, increases the peripheral blood content of effector and regulatory T cells and may have beneficial effects on cardiac allograft vasculopathy. The aim of the current study was to evaluate its effects in a murine aortic allograft model using different application procedures. Allogeneic donor aorta grafts (n = 8/group) from C57BL/6 mice(H2b) were abdominally transplanted into CBA mice (H2k). Plerixafor application was performed either continuously for 14 d using abdominally implanted osmotic pumps (1 mg/kg/d) or i.p. with a single dose (1 and 5 mg/kg) on day 0 or pulsed injections of 1 mg/kg on days 0, 7, 14, and 21. Cell distribution was monitored by FACS. Aortic grafts were evaluated for neointima development by Elastica-van-Gieson on day 30. Immunofluorescence and intragraft gene expression analysis were performed. On day 14, significantly fewer hematopoietic stem cells were found in the bone marrow of all plerixafor-treated mice. In the pulsed application group, significantly more hematopoietic stem cells were found in the peripheral blood on day 14 (0.045 ± 0.002%; p < 0.01 [pulsed]; versus 0.0068 ± 0.002% [control]) and also more regulatory T cells. PCR revealed lower inflammatory cytokines. The luminal occlusion was significantly reduced in the pulsed treated group (33.65 ± 8.84 versus 53.13 ± 12.41) going along with decreased neointimal CD4+ T cell and plasmacytoid dendritic cell infiltration, as well as less smooth muscle cell proliferation. The application of plerixafor attenuates chronic rejection in aortic allografts via immunomodulatory effects. Injection of repeated low-dose plerixafor is the most effective application form in the aortic transplant model.</description><subject>Allografts</subject><subject>Animals</subject><subject>Aorta - immunology</subject><subject>Benzylamines</subject><subject>Cyclams</subject><subject>Graft Rejection - immunology</subject><subject>Graft Rejection - prevention & control</subject><subject>Hematopoietic Stem Cell Mobilization - methods</subject><subject>Heterocyclic Compounds - administration & dosage</subject><subject>Heterocyclic Compounds - pharmacology</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Inbred CBA</subject><subject>Neointima - immunology</subject><subject>Receptors, CXCR4 - antagonists & inhibitors</subject><subject>T-Lymphocytes, Regulatory - immunology</subject><subject>Transplantation, Homologous</subject><issn>0022-1767</issn><issn>1550-6606</issn><issn>1550-6606</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo9kDtPwzAURi0EoqWwMyGPLCnXjzjNGCJeUhGoKogtchwHUpw42I5E_z1BLUx3OefT1UHonMCcA0-vNk3bDp01c8oABKMHaEriGCIhQByiKQClEUlEMkEn3m9gZIDyYzRhKVuMCpmiaqV7LYOucP6Wrzi-NlZ9ykrjcoufjXbNt6ytw1kIuhtGzuO1k53vjewCfpVeDcb2MnxscdPhx8E1ncaZdaFRODPGvjtZB3-KjmppvD7b3xl6ub1Z5_fR8unuIc-WkSILGiIWp2nKK1CJ5qSmEHMpRF0yEivJKkpTmXJScpWUgnIuJIlrQUcopgsoSaLYDF3udntnvwbtQ9E2XmkzPqvt4AtGCI8BCE9GFHaoctZ7p-uid00r3bYgUPy2Lf7aFvu2o3KxXx_KVlf_wl9M9gNRJnaP</recordid><startdate>20241115</startdate><enddate>20241115</enddate><creator>Theil, Frank</creator><creator>Kuckhahn, Annika</creator><creator>Hörning, André</creator><creator>Völkl, Simon</creator><creator>Knab, Katharina</creator><creator>Fritz, Niklas</creator><creator>Gräbner, Cindy</creator><creator>Ramsperger-Gleixner, Martina</creator><creator>Weyand, Michael</creator><creator>Heim, Christian</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0009-0001-0533-7214</orcidid><orcidid>https://orcid.org/0009-0002-2940-9160</orcidid><orcidid>https://orcid.org/0009-0001-9533-805X</orcidid><orcidid>https://orcid.org/0000-0001-5884-5856</orcidid><orcidid>https://orcid.org/0000-0001-6241-7168</orcidid></search><sort><creationdate>20241115</creationdate><title>Repeated CXCR4 Blockade by Plerixafor Attenuates Transplant Vasculopathy in Murine Aortic Allografts</title><author>Theil, Frank ; Kuckhahn, Annika ; Hörning, André ; Völkl, Simon ; Knab, Katharina ; Fritz, Niklas ; Gräbner, Cindy ; Ramsperger-Gleixner, Martina ; Weyand, Michael ; Heim, Christian</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c182t-359994d0c7e41f2054a66fb315ca3d229a941b4c7b62446a15f6254a5280b17c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Allografts</topic><topic>Animals</topic><topic>Aorta - immunology</topic><topic>Benzylamines</topic><topic>Cyclams</topic><topic>Graft Rejection - immunology</topic><topic>Graft Rejection - prevention & control</topic><topic>Hematopoietic Stem Cell Mobilization - methods</topic><topic>Heterocyclic Compounds - administration & dosage</topic><topic>Heterocyclic Compounds - pharmacology</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Inbred CBA</topic><topic>Neointima - immunology</topic><topic>Receptors, CXCR4 - antagonists & inhibitors</topic><topic>T-Lymphocytes, Regulatory - immunology</topic><topic>Transplantation, Homologous</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Theil, Frank</creatorcontrib><creatorcontrib>Kuckhahn, Annika</creatorcontrib><creatorcontrib>Hörning, André</creatorcontrib><creatorcontrib>Völkl, Simon</creatorcontrib><creatorcontrib>Knab, Katharina</creatorcontrib><creatorcontrib>Fritz, Niklas</creatorcontrib><creatorcontrib>Gräbner, Cindy</creatorcontrib><creatorcontrib>Ramsperger-Gleixner, Martina</creatorcontrib><creatorcontrib>Weyand, Michael</creatorcontrib><creatorcontrib>Heim, Christian</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>The Journal of immunology (1950)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Theil, Frank</au><au>Kuckhahn, Annika</au><au>Hörning, André</au><au>Völkl, Simon</au><au>Knab, Katharina</au><au>Fritz, Niklas</au><au>Gräbner, Cindy</au><au>Ramsperger-Gleixner, Martina</au><au>Weyand, Michael</au><au>Heim, Christian</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Repeated CXCR4 Blockade by Plerixafor Attenuates Transplant Vasculopathy in Murine Aortic Allografts</atitle><jtitle>The Journal of immunology (1950)</jtitle><addtitle>J Immunol</addtitle><date>2024-11-15</date><risdate>2024</risdate><volume>213</volume><issue>10</issue><spage>1542</spage><epage>1552</epage><pages>1542-1552</pages><issn>0022-1767</issn><issn>1550-6606</issn><eissn>1550-6606</eissn><abstract>Plerixafor, a hematopoietic stem cell mobilization agent, increases the peripheral blood content of effector and regulatory T cells and may have beneficial effects on cardiac allograft vasculopathy. The aim of the current study was to evaluate its effects in a murine aortic allograft model using different application procedures. Allogeneic donor aorta grafts (n = 8/group) from C57BL/6 mice(H2b) were abdominally transplanted into CBA mice (H2k). Plerixafor application was performed either continuously for 14 d using abdominally implanted osmotic pumps (1 mg/kg/d) or i.p. with a single dose (1 and 5 mg/kg) on day 0 or pulsed injections of 1 mg/kg on days 0, 7, 14, and 21. Cell distribution was monitored by FACS. Aortic grafts were evaluated for neointima development by Elastica-van-Gieson on day 30. Immunofluorescence and intragraft gene expression analysis were performed. On day 14, significantly fewer hematopoietic stem cells were found in the bone marrow of all plerixafor-treated mice. In the pulsed application group, significantly more hematopoietic stem cells were found in the peripheral blood on day 14 (0.045 ± 0.002%; p < 0.01 [pulsed]; versus 0.0068 ± 0.002% [control]) and also more regulatory T cells. PCR revealed lower inflammatory cytokines. The luminal occlusion was significantly reduced in the pulsed treated group (33.65 ± 8.84 versus 53.13 ± 12.41) going along with decreased neointimal CD4+ T cell and plasmacytoid dendritic cell infiltration, as well as less smooth muscle cell proliferation. The application of plerixafor attenuates chronic rejection in aortic allografts via immunomodulatory effects. Injection of repeated low-dose plerixafor is the most effective application form in the aortic transplant model.</abstract><cop>United States</cop><pmid>39382301</pmid><doi>10.4049/jimmunol.2300632</doi><tpages>11</tpages><orcidid>https://orcid.org/0009-0001-0533-7214</orcidid><orcidid>https://orcid.org/0009-0002-2940-9160</orcidid><orcidid>https://orcid.org/0009-0001-9533-805X</orcidid><orcidid>https://orcid.org/0000-0001-5884-5856</orcidid><orcidid>https://orcid.org/0000-0001-6241-7168</orcidid></addata></record> |
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| ispartof | The Journal of immunology (1950), 2024-11, Vol.213 (10), p.1542-1552 |
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| subjects | Allografts Animals Aorta - immunology Benzylamines Cyclams Graft Rejection - immunology Graft Rejection - prevention & control Hematopoietic Stem Cell Mobilization - methods Heterocyclic Compounds - administration & dosage Heterocyclic Compounds - pharmacology Male Mice Mice, Inbred C57BL Mice, Inbred CBA Neointima - immunology Receptors, CXCR4 - antagonists & inhibitors T-Lymphocytes, Regulatory - immunology Transplantation, Homologous |
| title | Repeated CXCR4 Blockade by Plerixafor Attenuates Transplant Vasculopathy in Murine Aortic Allografts |
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