The Alternative Receptor for Complement Component 5a, C5aR2, Conveys Neuroprotection in Traumatic Spinal Cord Injury
This study investigated the role of the alternative receptor for complement activation fragment C5a, C5aR2, in secondary inflammatory pathology after contusive spinal cord injury (SCI) in mice. C5ar2 mice exhibited decreased intraparenchymal tumor necrosis factor alpha and interleukin-6 acutely post...
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| Veröffentlicht in: | Journal of neurotrauma 2017-06, Vol.34 (12), p.2075-2085 |
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| creator | Biggins, Patrick J C Brennan, Faith H Taylor, Stephen M Woodruff, Trent M Ruitenberg, Marc J |
| description | This study investigated the role of the alternative receptor for complement activation fragment C5a, C5aR2, in secondary inflammatory pathology after contusive spinal cord injury (SCI) in mice. C5ar2
mice exhibited decreased intraparenchymal tumor necrosis factor alpha and interleukin-6 acutely post-injury, but these reductions did not translate into improved outcomes. We show that loss of C5aR2 leads to increased lesion volumes, reduced myelin sparing, and significantly worsened recovery from SCI in C5ar2
animals compared to wild-type (WT) controls. Loss of C5aR2 did not alter leukocyte mobilization from the bone marrow in response to SCI, and neutrophil recruitment/presence at the lesion site was also not different between genotypes. Acute treatment of SCI mice with the selective C5aR1 antagonist, PMX205, improved SCI outcomes, compared to vehicle controls, and, importantly, fully alleviated the worsened recovery of C5ar2
mice compared to their WT counterparts. Collectively, these findings indicate that C5aR2 is neuroprotective and a novel target to restrain injurious C5a signaling after a major neurotraumatic event. |
| doi_str_mv | 10.1089/neu.2016.4701 |
| format | Article |
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mice exhibited decreased intraparenchymal tumor necrosis factor alpha and interleukin-6 acutely post-injury, but these reductions did not translate into improved outcomes. We show that loss of C5aR2 leads to increased lesion volumes, reduced myelin sparing, and significantly worsened recovery from SCI in C5ar2
animals compared to wild-type (WT) controls. Loss of C5aR2 did not alter leukocyte mobilization from the bone marrow in response to SCI, and neutrophil recruitment/presence at the lesion site was also not different between genotypes. Acute treatment of SCI mice with the selective C5aR1 antagonist, PMX205, improved SCI outcomes, compared to vehicle controls, and, importantly, fully alleviated the worsened recovery of C5ar2
mice compared to their WT counterparts. Collectively, these findings indicate that C5aR2 is neuroprotective and a novel target to restrain injurious C5a signaling after a major neurotraumatic event.</description><identifier>ISSN: 0897-7151</identifier><identifier>EISSN: 1557-9042</identifier><identifier>DOI: 10.1089/neu.2016.4701</identifier><identifier>PMID: 28173736</identifier><language>eng</language><publisher>United States: Mary Ann Liebert, Inc</publisher><subject>Animals ; Bone marrow ; Complement activation ; Complement component C5a ; Cytokines ; Disease Models, Animal ; Female ; Genotypes ; Inflammation ; Interleukin 6 ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Myelin ; Neuroprotection ; Pathology ; Peptides, Cyclic - pharmacology ; Receptor, Anaphylatoxin C5a - antagonists & inhibitors ; Receptor, Anaphylatoxin C5a - deficiency ; Receptor, Anaphylatoxin C5a - physiology ; Rodents ; Spinal cord injuries ; Spinal Cord Injuries - drug therapy ; Spinal Cord Injuries - immunology ; Spinal Cord Injuries - metabolism ; Tumor necrosis factor</subject><ispartof>Journal of neurotrauma, 2017-06, Vol.34 (12), p.2075-2085</ispartof><rights>(©) Copyright 2017, Mary Ann Liebert, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c321t-d4865cd29355a1271c16cf10f2beec30a270f8edb3aed2a85bfc246d9a22be4d3</citedby><cites>FETCH-LOGICAL-c321t-d4865cd29355a1271c16cf10f2beec30a270f8edb3aed2a85bfc246d9a22be4d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28173736$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Biggins, Patrick J C</creatorcontrib><creatorcontrib>Brennan, Faith H</creatorcontrib><creatorcontrib>Taylor, Stephen M</creatorcontrib><creatorcontrib>Woodruff, Trent M</creatorcontrib><creatorcontrib>Ruitenberg, Marc J</creatorcontrib><title>The Alternative Receptor for Complement Component 5a, C5aR2, Conveys Neuroprotection in Traumatic Spinal Cord Injury</title><title>Journal of neurotrauma</title><addtitle>J Neurotrauma</addtitle><description>This study investigated the role of the alternative receptor for complement activation fragment C5a, C5aR2, in secondary inflammatory pathology after contusive spinal cord injury (SCI) in mice. C5ar2
mice exhibited decreased intraparenchymal tumor necrosis factor alpha and interleukin-6 acutely post-injury, but these reductions did not translate into improved outcomes. We show that loss of C5aR2 leads to increased lesion volumes, reduced myelin sparing, and significantly worsened recovery from SCI in C5ar2
animals compared to wild-type (WT) controls. Loss of C5aR2 did not alter leukocyte mobilization from the bone marrow in response to SCI, and neutrophil recruitment/presence at the lesion site was also not different between genotypes. Acute treatment of SCI mice with the selective C5aR1 antagonist, PMX205, improved SCI outcomes, compared to vehicle controls, and, importantly, fully alleviated the worsened recovery of C5ar2
mice compared to their WT counterparts. Collectively, these findings indicate that C5aR2 is neuroprotective and a novel target to restrain injurious C5a signaling after a major neurotraumatic event.</description><subject>Animals</subject><subject>Bone marrow</subject><subject>Complement activation</subject><subject>Complement component C5a</subject><subject>Cytokines</subject><subject>Disease Models, Animal</subject><subject>Female</subject><subject>Genotypes</subject><subject>Inflammation</subject><subject>Interleukin 6</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Myelin</subject><subject>Neuroprotection</subject><subject>Pathology</subject><subject>Peptides, Cyclic - pharmacology</subject><subject>Receptor, Anaphylatoxin C5a - antagonists & inhibitors</subject><subject>Receptor, Anaphylatoxin C5a - deficiency</subject><subject>Receptor, Anaphylatoxin C5a - physiology</subject><subject>Rodents</subject><subject>Spinal cord injuries</subject><subject>Spinal Cord Injuries - drug therapy</subject><subject>Spinal Cord Injuries - immunology</subject><subject>Spinal Cord Injuries - metabolism</subject><subject>Tumor necrosis factor</subject><issn>0897-7151</issn><issn>1557-9042</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNpdkUFr3DAQhUVpSDZpjr0GQS89xBuNZEn2MSxNGggNbLdno5XHxIstOZIc2H8fbTfpoYfhDczHY3iPkK_AlsCq-sbhvOQM1LLUDD6RBUipi5qV_DNZ5LsuNEg4I-cx7hgDobg-JWe8Ai20UAuSNs9Ib4eEwZnUvyJdo8Up-UC7PCs_TgOO6NLf1bvDJs01XUmz5lm8e8V9pL9wDn4KPqFNvXe0d3QTzDxmS0t_T70zQ2ZDSx_cbg77L-SkM0PEy3e9IH_ufmxWP4vHp_uH1e1jYQWHVLRlpaRteS2kNMA1WFC2A9bxLaIVzHDNugrbrTDYclPJbWd5qdra8EyUrbgg34---bWXGWNqxj5aHAbj0M-xgUopXnNVqYx--w_d-TlnMmSqZgoUSC4zVRwpG3yMAbtmCv1owr4B1hzqaHIdzaGO5lBH5q_eXeftiO0_-iN_8QZ39oY1</recordid><startdate>20170615</startdate><enddate>20170615</enddate><creator>Biggins, Patrick J C</creator><creator>Brennan, Faith H</creator><creator>Taylor, Stephen M</creator><creator>Woodruff, Trent M</creator><creator>Ruitenberg, Marc J</creator><general>Mary Ann Liebert, Inc</general><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>3V.</scope><scope>7RV</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88G</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>M1P</scope><scope>M2M</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PSYQQ</scope><scope>Q9U</scope><scope>7X8</scope></search><sort><creationdate>20170615</creationdate><title>The Alternative Receptor for Complement Component 5a, C5aR2, Conveys Neuroprotection in Traumatic Spinal Cord Injury</title><author>Biggins, Patrick J C ; Brennan, Faith H ; Taylor, Stephen M ; Woodruff, Trent M ; Ruitenberg, Marc J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c321t-d4865cd29355a1271c16cf10f2beec30a270f8edb3aed2a85bfc246d9a22be4d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Animals</topic><topic>Bone marrow</topic><topic>Complement activation</topic><topic>Complement component C5a</topic><topic>Cytokines</topic><topic>Disease Models, Animal</topic><topic>Female</topic><topic>Genotypes</topic><topic>Inflammation</topic><topic>Interleukin 6</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout</topic><topic>Myelin</topic><topic>Neuroprotection</topic><topic>Pathology</topic><topic>Peptides, Cyclic - pharmacology</topic><topic>Receptor, Anaphylatoxin C5a - antagonists & inhibitors</topic><topic>Receptor, Anaphylatoxin C5a - deficiency</topic><topic>Receptor, Anaphylatoxin C5a - physiology</topic><topic>Rodents</topic><topic>Spinal cord injuries</topic><topic>Spinal Cord Injuries - drug therapy</topic><topic>Spinal Cord Injuries - immunology</topic><topic>Spinal Cord Injuries - metabolism</topic><topic>Tumor necrosis factor</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Biggins, Patrick J C</creatorcontrib><creatorcontrib>Brennan, Faith H</creatorcontrib><creatorcontrib>Taylor, Stephen M</creatorcontrib><creatorcontrib>Woodruff, Trent M</creatorcontrib><creatorcontrib>Ruitenberg, Marc J</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Psychology Database (Alumni)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Psychology Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest One Psychology</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of neurotrauma</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Biggins, Patrick J C</au><au>Brennan, Faith H</au><au>Taylor, Stephen M</au><au>Woodruff, Trent M</au><au>Ruitenberg, Marc J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The Alternative Receptor for Complement Component 5a, C5aR2, Conveys Neuroprotection in Traumatic Spinal Cord Injury</atitle><jtitle>Journal of neurotrauma</jtitle><addtitle>J Neurotrauma</addtitle><date>2017-06-15</date><risdate>2017</risdate><volume>34</volume><issue>12</issue><spage>2075</spage><epage>2085</epage><pages>2075-2085</pages><issn>0897-7151</issn><eissn>1557-9042</eissn><abstract>This study investigated the role of the alternative receptor for complement activation fragment C5a, C5aR2, in secondary inflammatory pathology after contusive spinal cord injury (SCI) in mice. C5ar2
mice exhibited decreased intraparenchymal tumor necrosis factor alpha and interleukin-6 acutely post-injury, but these reductions did not translate into improved outcomes. We show that loss of C5aR2 leads to increased lesion volumes, reduced myelin sparing, and significantly worsened recovery from SCI in C5ar2
animals compared to wild-type (WT) controls. Loss of C5aR2 did not alter leukocyte mobilization from the bone marrow in response to SCI, and neutrophil recruitment/presence at the lesion site was also not different between genotypes. Acute treatment of SCI mice with the selective C5aR1 antagonist, PMX205, improved SCI outcomes, compared to vehicle controls, and, importantly, fully alleviated the worsened recovery of C5ar2
mice compared to their WT counterparts. Collectively, these findings indicate that C5aR2 is neuroprotective and a novel target to restrain injurious C5a signaling after a major neurotraumatic event.</abstract><cop>United States</cop><pub>Mary Ann Liebert, Inc</pub><pmid>28173736</pmid><doi>10.1089/neu.2016.4701</doi><tpages>11</tpages></addata></record> |
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| ispartof | Journal of neurotrauma, 2017-06, Vol.34 (12), p.2075-2085 |
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| source | MEDLINE; Alma/SFX Local Collection |
| subjects | Animals Bone marrow Complement activation Complement component C5a Cytokines Disease Models, Animal Female Genotypes Inflammation Interleukin 6 Mice Mice, Inbred C57BL Mice, Knockout Myelin Neuroprotection Pathology Peptides, Cyclic - pharmacology Receptor, Anaphylatoxin C5a - antagonists & inhibitors Receptor, Anaphylatoxin C5a - deficiency Receptor, Anaphylatoxin C5a - physiology Rodents Spinal cord injuries Spinal Cord Injuries - drug therapy Spinal Cord Injuries - immunology Spinal Cord Injuries - metabolism Tumor necrosis factor |
| title | The Alternative Receptor for Complement Component 5a, C5aR2, Conveys Neuroprotection in Traumatic Spinal Cord Injury |
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