The role of the beta chemokines in experimental obliterative bronchiolitis

Beta chemokines have been implicated in cardiac and renal allograft rejection. This study determined if antibody antagonization of beta chemokines conferred protection against the development of experimental obliterative bronchiolitis (OB) in a heterotopic rat tracheal allograft model. Rat tracheas...

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Veröffentlicht in:Experimental and molecular pathology 2003-12, Vol.75 (3), p.210-216
Hauptverfasser: Farivar, Alexander S, Krishnadasan, Baiya, Naidu, Babu V, Woolley, Steven M, Mulligan, Michael S
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container_start_page 210
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creator Farivar, Alexander S
Krishnadasan, Baiya
Naidu, Babu V
Woolley, Steven M
Mulligan, Michael S
description Beta chemokines have been implicated in cardiac and renal allograft rejection. This study determined if antibody antagonization of beta chemokines conferred protection against the development of experimental obliterative bronchiolitis (OB) in a heterotopic rat tracheal allograft model. Rat tracheas were transplanted from Brown-Norway or Lewis donors into Lewis recipients. Rats received 200 μg/day of either anti-RANTES or anti-MCP-1 antibody for 14 days. Luminal obstruction and epithelial loss were calculated. Northern blots for MCP-1 and RANTES mRNA expression were performed, and immunohistochemistry for chemokine protein localization. There was a significant increase in airway obstruction in allografts compared to isografts ( P < 0.001). Antibody-treated allografts demonstrated an amelioration of airway obstruction from 58% (vehicle allografts) to 26% (anti-RANTES) and 12% (anti-MCP-1), both of which were significant ( P < 0.001). Epithelial preservation was increased in both antibody-treated groups ( P < 0.001), and increased expression of MCP-1 and RANTES mRNA was present in tracheal allografts by Day 2 and maximal by Day 6. Beta chemokines are expressed during the development of experimental OB, as MCP-1 and RANTES mRNA expression increased with time from transplantation. Both MCP-1 and RANTES are functional in the formation of the fibroproliferative response that characterizes OB in this model, and their antagonization conferred protection against airway obstruction and epithelial loss.
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Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques</topic><topic>Pneumology</topic><topic>RANTES</topic><topic>Rat tracheal allografts</topic><topic>Rats</topic><topic>RNA, Messenger - analysis</topic><topic>Trachea - pathology</topic><topic>Trachea - transplantation</topic><topic>Transplantation, Homologous - immunology</topic><topic>Transplantation, Isogeneic - immunology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Farivar, Alexander S</creatorcontrib><creatorcontrib>Krishnadasan, Baiya</creatorcontrib><creatorcontrib>Naidu, Babu V</creatorcontrib><creatorcontrib>Woolley, Steven M</creatorcontrib><creatorcontrib>Mulligan, Michael S</creatorcontrib><collection>Pascal-Francis</collection><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>Experimental and molecular pathology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Farivar, Alexander S</au><au>Krishnadasan, Baiya</au><au>Naidu, Babu V</au><au>Woolley, Steven M</au><au>Mulligan, Michael S</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The role of the beta chemokines in experimental obliterative bronchiolitis</atitle><jtitle>Experimental and molecular pathology</jtitle><addtitle>Exp Mol Pathol</addtitle><date>2003-12-01</date><risdate>2003</risdate><volume>75</volume><issue>3</issue><spage>210</spage><epage>216</epage><pages>210-216</pages><issn>0014-4800</issn><eissn>1096-0945</eissn><coden>EXMPA6</coden><abstract>Beta chemokines have been implicated in cardiac and renal allograft rejection. This study determined if antibody antagonization of beta chemokines conferred protection against the development of experimental obliterative bronchiolitis (OB) in a heterotopic rat tracheal allograft model. Rat tracheas were transplanted from Brown-Norway or Lewis donors into Lewis recipients. Rats received 200 μg/day of either anti-RANTES or anti-MCP-1 antibody for 14 days. Luminal obstruction and epithelial loss were calculated. Northern blots for MCP-1 and RANTES mRNA expression were performed, and immunohistochemistry for chemokine protein localization. There was a significant increase in airway obstruction in allografts compared to isografts ( P &lt; 0.001). Antibody-treated allografts demonstrated an amelioration of airway obstruction from 58% (vehicle allografts) to 26% (anti-RANTES) and 12% (anti-MCP-1), both of which were significant ( P &lt; 0.001). Epithelial preservation was increased in both antibody-treated groups ( P &lt; 0.001), and increased expression of MCP-1 and RANTES mRNA was present in tracheal allografts by Day 2 and maximal by Day 6. Beta chemokines are expressed during the development of experimental OB, as MCP-1 and RANTES mRNA expression increased with time from transplantation. Both MCP-1 and RANTES are functional in the formation of the fibroproliferative response that characterizes OB in this model, and their antagonization conferred protection against airway obstruction and epithelial loss.</abstract><cop>Amsterdam</cop><pub>Elsevier Inc</pub><pmid>14611812</pmid><doi>10.1016/S0014-4800(03)00093-5</doi><tpages>7</tpages></addata></record>
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subjects Animals
Antibodies - therapeutic use
Beta chemokines
Biological and medical sciences
Blotting, Northern
Bronchiolitis Obliterans - metabolism
Bronchiolitis Obliterans - prevention & control
Chemokine CCL2 - immunology
Chemokine CCL5 - immunology
Chemokines, CC - immunology
Chemokines, CC - metabolism
Chronic obstructive pulmonary disease, asthma
Disease Models, Animal
Graft Rejection - metabolism
Graft Rejection - pathology
Heterotopic tracheal transplantation
Immunohistochemistry
Investigative techniques, diagnostic techniques (general aspects)
Lung transplantation
Male
MCP-1
Medical sciences
Obliterative bronchiolitis
Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques
Pneumology
RANTES
Rat tracheal allografts
Rats
RNA, Messenger - analysis
Trachea - pathology
Trachea - transplantation
Transplantation, Homologous - immunology
Transplantation, Isogeneic - immunology
title The role of the beta chemokines in experimental obliterative bronchiolitis
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