Conformational activation of CD11b without shedding of L-selectin on circulating human neutrophils
Membrane‐activated complex 1 (Mac‐1; CD11b/CD18) is a β2 integrin implicated in the pathophysiology of neutrophil‐mediated tissue injury whose functional capacity is determined by stimulus‐induced conformational activation rather than up‐regulation. Mac‐1 up‐regulation and conformational activation,...
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| Veröffentlicht in: | Journal of leukocyte biology 2007-11, Vol.82 (5), p.1115-1125 |
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| container_title | Journal of leukocyte biology |
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| creator | Orr, Y. Taylor, J. M. Cartland, S. Bannon, P. G. Geczy, C. Kritharides, L. |
| description | Membrane‐activated complex 1 (Mac‐1; CD11b/CD18) is a β2 integrin implicated in the pathophysiology of neutrophil‐mediated tissue injury whose functional capacity is determined by stimulus‐induced conformational activation rather than up‐regulation. Mac‐1 up‐regulation and conformational activation, together with shedding of L‐selectin, are reported after in vitro neutrophil activation. However, their regulation on circulating human neutrophils during acute inflammation is unclear. Using flow cytometry, we investigated neutrophil expression of Mac‐1, its activation‐reporter neo‐epitope CBRM1/5, and L‐selectin during the inflammatory stimulus of cardiac surgery. A subpopulation of circulating neutrophils expressed CBRM1/5 (CBRM1/5+) under basal conditions (6.28±2.59%) and was persistently expanded (9.95±4.0%–15.2±4.2%; P |
| doi_str_mv | 10.1189/jlb.0906545 |
| format | Article |
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M. ; Cartland, S. ; Bannon, P. G. ; Geczy, C. ; Kritharides, L.</creator><creatorcontrib>Orr, Y. ; Taylor, J. M. ; Cartland, S. ; Bannon, P. G. ; Geczy, C. ; Kritharides, L.</creatorcontrib><description>Membrane‐activated complex 1 (Mac‐1; CD11b/CD18) is a β2 integrin implicated in the pathophysiology of neutrophil‐mediated tissue injury whose functional capacity is determined by stimulus‐induced conformational activation rather than up‐regulation. Mac‐1 up‐regulation and conformational activation, together with shedding of L‐selectin, are reported after in vitro neutrophil activation. However, their regulation on circulating human neutrophils during acute inflammation is unclear. Using flow cytometry, we investigated neutrophil expression of Mac‐1, its activation‐reporter neo‐epitope CBRM1/5, and L‐selectin during the inflammatory stimulus of cardiac surgery. A subpopulation of circulating neutrophils expressed CBRM1/5 (CBRM1/5+) under basal conditions (6.28±2.59%) and was persistently expanded (9.95±4.0%–15.2±4.2%; P<0.0001) peri‐operatively, whereas total CD11b expression increased only transiently, intra‐operatively. L‐selectin expression was unchanged on CBRM1/5+ neutrophils, and soluble L‐selectin levels decreased intra‐operatively (P<0.01), indicating that L‐selectin was not shed. Increased CBRM1/5 expression without L‐selectin loss or CD11b up‐regulation was replicated in vitro by neutrophil stimulation with IL‐8, C3a, and platelet‐activating factor. Heparin, a known CD11b ligand, which is administered during cardiac surgery, markedly reduced neutrophil expression of conformationally active CD11b in vivo and in vitro, identifying a potential mechanism for its anti‐inflammatory properties. We conclude that conformational activation of CD11b occurs on circulating neutrophils in vivo and can occur in the absence of CD11b up‐regulation and L‐selectin shedding.</description><identifier>ISSN: 0741-5400</identifier><identifier>EISSN: 1938-3673</identifier><identifier>DOI: 10.1189/jlb.0906545</identifier><identifier>PMID: 17675559</identifier><language>eng</language><publisher>United States: Society for Leukocyte Biology</publisher><subject>adhesion molecules ; Adult ; Aged ; Aged, 80 and over ; Angina Pectoris - immunology ; Angina Pectoris - metabolism ; Angina Pectoris - surgery ; CD11b Antigen - chemistry ; CD11b Antigen - genetics ; CD11b Antigen - metabolism ; Chronic Disease ; Complement C3a - metabolism ; Coronary Artery Bypass ; Epitopes - immunology ; Epitopes - metabolism ; Female ; Flow Cytometry ; heparin ; Heparin - pharmacology ; Humans ; inflammation ; integrins ; Interleukin-8 - metabolism ; L-Selectin - metabolism ; Macrophage-1 Antigen - immunology ; Macrophage-1 Antigen - metabolism ; Male ; Middle Aged ; Neutrophil Activation ; Neutrophils - metabolism ; Platelet Activating Factor - metabolism ; Prospective Studies ; Protein Conformation ; Signal Transduction</subject><ispartof>Journal of leukocyte biology, 2007-11, Vol.82 (5), p.1115-1125</ispartof><rights>2007 Society for Leukocyte Biology</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3905-c22484bce1910f7015a38856bc47e38de6f12dca2ea93c772d18ca5032ddff353</citedby><cites>FETCH-LOGICAL-c3905-c22484bce1910f7015a38856bc47e38de6f12dca2ea93c772d18ca5032ddff353</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1189%2Fjlb.0906545$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1189%2Fjlb.0906545$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,778,782,1414,27911,27912,45561,45562</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17675559$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Orr, Y.</creatorcontrib><creatorcontrib>Taylor, J. M.</creatorcontrib><creatorcontrib>Cartland, S.</creatorcontrib><creatorcontrib>Bannon, P. G.</creatorcontrib><creatorcontrib>Geczy, C.</creatorcontrib><creatorcontrib>Kritharides, L.</creatorcontrib><title>Conformational activation of CD11b without shedding of L-selectin on circulating human neutrophils</title><title>Journal of leukocyte biology</title><addtitle>J Leukoc Biol</addtitle><description>Membrane‐activated complex 1 (Mac‐1; CD11b/CD18) is a β2 integrin implicated in the pathophysiology of neutrophil‐mediated tissue injury whose functional capacity is determined by stimulus‐induced conformational activation rather than up‐regulation. Mac‐1 up‐regulation and conformational activation, together with shedding of L‐selectin, are reported after in vitro neutrophil activation. However, their regulation on circulating human neutrophils during acute inflammation is unclear. Using flow cytometry, we investigated neutrophil expression of Mac‐1, its activation‐reporter neo‐epitope CBRM1/5, and L‐selectin during the inflammatory stimulus of cardiac surgery. A subpopulation of circulating neutrophils expressed CBRM1/5 (CBRM1/5+) under basal conditions (6.28±2.59%) and was persistently expanded (9.95±4.0%–15.2±4.2%; P<0.0001) peri‐operatively, whereas total CD11b expression increased only transiently, intra‐operatively. L‐selectin expression was unchanged on CBRM1/5+ neutrophils, and soluble L‐selectin levels decreased intra‐operatively (P<0.01), indicating that L‐selectin was not shed. Increased CBRM1/5 expression without L‐selectin loss or CD11b up‐regulation was replicated in vitro by neutrophil stimulation with IL‐8, C3a, and platelet‐activating factor. Heparin, a known CD11b ligand, which is administered during cardiac surgery, markedly reduced neutrophil expression of conformationally active CD11b in vivo and in vitro, identifying a potential mechanism for its anti‐inflammatory properties. We conclude that conformational activation of CD11b occurs on circulating neutrophils in vivo and can occur in the absence of CD11b up‐regulation and L‐selectin shedding.</description><subject>adhesion molecules</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Angina Pectoris - immunology</subject><subject>Angina Pectoris - metabolism</subject><subject>Angina Pectoris - surgery</subject><subject>CD11b Antigen - chemistry</subject><subject>CD11b Antigen - genetics</subject><subject>CD11b Antigen - metabolism</subject><subject>Chronic Disease</subject><subject>Complement C3a - metabolism</subject><subject>Coronary Artery Bypass</subject><subject>Epitopes - immunology</subject><subject>Epitopes - metabolism</subject><subject>Female</subject><subject>Flow Cytometry</subject><subject>heparin</subject><subject>Heparin - pharmacology</subject><subject>Humans</subject><subject>inflammation</subject><subject>integrins</subject><subject>Interleukin-8 - metabolism</subject><subject>L-Selectin - metabolism</subject><subject>Macrophage-1 Antigen - immunology</subject><subject>Macrophage-1 Antigen - metabolism</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Neutrophil Activation</subject><subject>Neutrophils - metabolism</subject><subject>Platelet Activating Factor - metabolism</subject><subject>Prospective Studies</subject><subject>Protein Conformation</subject><subject>Signal Transduction</subject><issn>0741-5400</issn><issn>1938-3673</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqF0LFv3CAUBnBUJepd0k7dK09ZKic8MAaPidumrU7K0s4IYxxzwuYCdqz89-FyJ6VTMiH0fnzofQh9AXwJIKqrrWsucYVLVrAPaA0VFTktOT1Ba8wLyFmB8QqdxbjFGFNS4o9oBbzkjLFqjZraj50Pg5qsH5XLlJ7s48sl811WfwdossVOvZ-nLPambe14v59s8micSTi5MdM26NmlZ2nYz4Mas9HMU_C73rr4CZ12ykXz-Xieo38_f_ytf-Wbu9vf9fUm17TCLNeEFKJotIEKcMcxMEWFYGWjC26oaE3ZAWm1IkZVVHNOWhBasbRS23YdZfQcXRxyd8E_zCZOcrBRG-fUaPwcZSkKWlBC3oUEM8442Sd-O0AdfIzBdHIX7KDCkwQs993L1L08dp_012Ps3AymfbXHshPAB7BYZ57eypJ_NjcA8N9Ovb3vFxuMjINyLv1A5LIsgkgmX-AzlxKcCQ</recordid><startdate>20071101</startdate><enddate>20071101</enddate><creator>Orr, Y.</creator><creator>Taylor, J. M.</creator><creator>Cartland, S.</creator><creator>Bannon, P. G.</creator><creator>Geczy, C.</creator><creator>Kritharides, L.</creator><general>Society for Leukocyte Biology</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>7T5</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>20071101</creationdate><title>Conformational activation of CD11b without shedding of L-selectin on circulating human neutrophils</title><author>Orr, Y. ; Taylor, J. M. ; Cartland, S. ; Bannon, P. G. ; Geczy, C. ; Kritharides, L.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3905-c22484bce1910f7015a38856bc47e38de6f12dca2ea93c772d18ca5032ddff353</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>adhesion molecules</topic><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Angina Pectoris - immunology</topic><topic>Angina Pectoris - metabolism</topic><topic>Angina Pectoris - surgery</topic><topic>CD11b Antigen - chemistry</topic><topic>CD11b Antigen - genetics</topic><topic>CD11b Antigen - metabolism</topic><topic>Chronic Disease</topic><topic>Complement C3a - metabolism</topic><topic>Coronary Artery Bypass</topic><topic>Epitopes - immunology</topic><topic>Epitopes - metabolism</topic><topic>Female</topic><topic>Flow Cytometry</topic><topic>heparin</topic><topic>Heparin - pharmacology</topic><topic>Humans</topic><topic>inflammation</topic><topic>integrins</topic><topic>Interleukin-8 - metabolism</topic><topic>L-Selectin - metabolism</topic><topic>Macrophage-1 Antigen - immunology</topic><topic>Macrophage-1 Antigen - metabolism</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Neutrophil Activation</topic><topic>Neutrophils - metabolism</topic><topic>Platelet Activating Factor - metabolism</topic><topic>Prospective Studies</topic><topic>Protein Conformation</topic><topic>Signal Transduction</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Orr, Y.</creatorcontrib><creatorcontrib>Taylor, J. M.</creatorcontrib><creatorcontrib>Cartland, S.</creatorcontrib><creatorcontrib>Bannon, P. G.</creatorcontrib><creatorcontrib>Geczy, C.</creatorcontrib><creatorcontrib>Kritharides, L.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of leukocyte biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Orr, Y.</au><au>Taylor, J. M.</au><au>Cartland, S.</au><au>Bannon, P. G.</au><au>Geczy, C.</au><au>Kritharides, L.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Conformational activation of CD11b without shedding of L-selectin on circulating human neutrophils</atitle><jtitle>Journal of leukocyte biology</jtitle><addtitle>J Leukoc Biol</addtitle><date>2007-11-01</date><risdate>2007</risdate><volume>82</volume><issue>5</issue><spage>1115</spage><epage>1125</epage><pages>1115-1125</pages><issn>0741-5400</issn><eissn>1938-3673</eissn><abstract>Membrane‐activated complex 1 (Mac‐1; CD11b/CD18) is a β2 integrin implicated in the pathophysiology of neutrophil‐mediated tissue injury whose functional capacity is determined by stimulus‐induced conformational activation rather than up‐regulation. Mac‐1 up‐regulation and conformational activation, together with shedding of L‐selectin, are reported after in vitro neutrophil activation. However, their regulation on circulating human neutrophils during acute inflammation is unclear. Using flow cytometry, we investigated neutrophil expression of Mac‐1, its activation‐reporter neo‐epitope CBRM1/5, and L‐selectin during the inflammatory stimulus of cardiac surgery. A subpopulation of circulating neutrophils expressed CBRM1/5 (CBRM1/5+) under basal conditions (6.28±2.59%) and was persistently expanded (9.95±4.0%–15.2±4.2%; P<0.0001) peri‐operatively, whereas total CD11b expression increased only transiently, intra‐operatively. L‐selectin expression was unchanged on CBRM1/5+ neutrophils, and soluble L‐selectin levels decreased intra‐operatively (P<0.01), indicating that L‐selectin was not shed. Increased CBRM1/5 expression without L‐selectin loss or CD11b up‐regulation was replicated in vitro by neutrophil stimulation with IL‐8, C3a, and platelet‐activating factor. Heparin, a known CD11b ligand, which is administered during cardiac surgery, markedly reduced neutrophil expression of conformationally active CD11b in vivo and in vitro, identifying a potential mechanism for its anti‐inflammatory properties. We conclude that conformational activation of CD11b occurs on circulating neutrophils in vivo and can occur in the absence of CD11b up‐regulation and L‐selectin shedding.</abstract><cop>United States</cop><pub>Society for Leukocyte Biology</pub><pmid>17675559</pmid><doi>10.1189/jlb.0906545</doi><tpages>11</tpages></addata></record> |
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| subjects | adhesion molecules Adult Aged Aged, 80 and over Angina Pectoris - immunology Angina Pectoris - metabolism Angina Pectoris - surgery CD11b Antigen - chemistry CD11b Antigen - genetics CD11b Antigen - metabolism Chronic Disease Complement C3a - metabolism Coronary Artery Bypass Epitopes - immunology Epitopes - metabolism Female Flow Cytometry heparin Heparin - pharmacology Humans inflammation integrins Interleukin-8 - metabolism L-Selectin - metabolism Macrophage-1 Antigen - immunology Macrophage-1 Antigen - metabolism Male Middle Aged Neutrophil Activation Neutrophils - metabolism Platelet Activating Factor - metabolism Prospective Studies Protein Conformation Signal Transduction |
| title | Conformational activation of CD11b without shedding of L-selectin on circulating human neutrophils |
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