NB1 mediates surface expression of the ANCA antigen proteinase 3 on human neutrophils
Antineutrophil cytoplasmic antibodies (ANCAs) with specificity for proteinase 3 (PR3) are central to a form of ANCA-associated vasculitis. Membrane PR3 (mPR3) is expressed only on a subset of neutrophils. The aim of this study was to determine the mechanism of PR3 surface expression on human neutrop...
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Veröffentlicht in: | Blood 2007-05, Vol.109 (10), p.4487-4493 |
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description | Antineutrophil cytoplasmic antibodies (ANCAs) with specificity for proteinase 3 (PR3) are central to a form of ANCA-associated vasculitis. Membrane PR3 (mPR3) is expressed only on a subset of neutrophils. The aim of this study was to determine the mechanism of PR3 surface expression on human neutrophils. Neutrophils were isolated from patients and healthy controls, and hematopoietic stem cells from cord blood served as a model of neutrophil differentiation. Surface expression was analyzed by flow cytometry and confocal microscopy, and proteins were analyzed by Western blot experiments. Neutrophil subsets were separated by magnetic cell sorting. Transfection experiments were carried out in HEK293 and HL60 cell lines. Using neutrophils from healthy donors, patients with vasculitis, and neutrophilic differentiated stem cells we found that mPR3 display was restricted to cells expressing neutrophil glycoprotein NB1, a glycosylphosphatidylinositol (GPI)–linked surface receptor. mPR3 expression was decreased by enzymatic removal of GPI anchors from cell membranes and was absent in a patient with paroxysmal nocturnal hemoglobinuria. PR3 and NB1 coimmunoprecipitated from and colocalized on the neutrophil plasma membrane. Transfection with NB1 resulted in specific PR3 surface binding in different cell types. We conclude that PR3 membrane expression on neutrophils is mediated by the NB1 receptor. |
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Membrane PR3 (mPR3) is expressed only on a subset of neutrophils. The aim of this study was to determine the mechanism of PR3 surface expression on human neutrophils. Neutrophils were isolated from patients and healthy controls, and hematopoietic stem cells from cord blood served as a model of neutrophil differentiation. Surface expression was analyzed by flow cytometry and confocal microscopy, and proteins were analyzed by Western blot experiments. Neutrophil subsets were separated by magnetic cell sorting. Transfection experiments were carried out in HEK293 and HL60 cell lines. Using neutrophils from healthy donors, patients with vasculitis, and neutrophilic differentiated stem cells we found that mPR3 display was restricted to cells expressing neutrophil glycoprotein NB1, a glycosylphosphatidylinositol (GPI)–linked surface receptor. mPR3 expression was decreased by enzymatic removal of GPI anchors from cell membranes and was absent in a patient with paroxysmal nocturnal hemoglobinuria. PR3 and NB1 coimmunoprecipitated from and colocalized on the neutrophil plasma membrane. Transfection with NB1 resulted in specific PR3 surface binding in different cell types. We conclude that PR3 membrane expression on neutrophils is mediated by the NB1 receptor.</description><identifier>ISSN: 0006-4971</identifier><identifier>EISSN: 1528-0020</identifier><identifier>DOI: 10.1182/blood-2006-10-055327</identifier><identifier>PMID: 17244676</identifier><language>eng</language><publisher>Washington, DC: Elsevier Inc</publisher><subject>Antibodies, Antineutrophil Cytoplasmic - immunology ; Antigens, Surface - metabolism ; Biological and medical sciences ; Cell Membrane - metabolism ; Cells, Cultured ; Fetal Blood - cytology ; Glycosylphosphatidylinositols - metabolism ; GPI-Linked Proteins ; Hematologic and hematopoietic diseases ; Hematopoietic Stem Cells - metabolism ; Humans ; Immunoprecipitation ; In Vitro Techniques ; Isoantigens - physiology ; Medical sciences ; Membrane Glycoproteins - physiology ; Myeloblastin - immunology ; Myeloblastin - metabolism ; Neutrophils - enzymology ; Neutrophils - metabolism ; Receptors, Cell Surface - physiology ; Transfection</subject><ispartof>Blood, 2007-05, Vol.109 (10), p.4487-4493</ispartof><rights>2007 American Society of Hematology</rights><rights>2007 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c502t-2384c5986ee1823d65cf5512d0354531bf9e3f3a17a8c1c2d1ff4ad5466cccc93</citedby><cites>FETCH-LOGICAL-c502t-2384c5986ee1823d65cf5512d0354531bf9e3f3a17a8c1c2d1ff4ad5466cccc93</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,782,786,27931,27932</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=18782426$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17244676$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>von Vietinghoff, Sibylle</creatorcontrib><creatorcontrib>Tunnemann, Gisela</creatorcontrib><creatorcontrib>Eulenberg, Claudia</creatorcontrib><creatorcontrib>Wellner, Maren</creatorcontrib><creatorcontrib>Cristina Cardoso, M.</creatorcontrib><creatorcontrib>Luft, Friedrich C.</creatorcontrib><creatorcontrib>Kettritz, Ralph</creatorcontrib><title>NB1 mediates surface expression of the ANCA antigen proteinase 3 on human neutrophils</title><title>Blood</title><addtitle>Blood</addtitle><description>Antineutrophil cytoplasmic antibodies (ANCAs) with specificity for proteinase 3 (PR3) are central to a form of ANCA-associated vasculitis. Membrane PR3 (mPR3) is expressed only on a subset of neutrophils. The aim of this study was to determine the mechanism of PR3 surface expression on human neutrophils. Neutrophils were isolated from patients and healthy controls, and hematopoietic stem cells from cord blood served as a model of neutrophil differentiation. Surface expression was analyzed by flow cytometry and confocal microscopy, and proteins were analyzed by Western blot experiments. Neutrophil subsets were separated by magnetic cell sorting. Transfection experiments were carried out in HEK293 and HL60 cell lines. Using neutrophils from healthy donors, patients with vasculitis, and neutrophilic differentiated stem cells we found that mPR3 display was restricted to cells expressing neutrophil glycoprotein NB1, a glycosylphosphatidylinositol (GPI)–linked surface receptor. mPR3 expression was decreased by enzymatic removal of GPI anchors from cell membranes and was absent in a patient with paroxysmal nocturnal hemoglobinuria. PR3 and NB1 coimmunoprecipitated from and colocalized on the neutrophil plasma membrane. Transfection with NB1 resulted in specific PR3 surface binding in different cell types. We conclude that PR3 membrane expression on neutrophils is mediated by the NB1 receptor.</description><subject>Antibodies, Antineutrophil Cytoplasmic - immunology</subject><subject>Antigens, Surface - metabolism</subject><subject>Biological and medical sciences</subject><subject>Cell Membrane - metabolism</subject><subject>Cells, Cultured</subject><subject>Fetal Blood - cytology</subject><subject>Glycosylphosphatidylinositols - metabolism</subject><subject>GPI-Linked Proteins</subject><subject>Hematologic and hematopoietic diseases</subject><subject>Hematopoietic Stem Cells - metabolism</subject><subject>Humans</subject><subject>Immunoprecipitation</subject><subject>In Vitro Techniques</subject><subject>Isoantigens - physiology</subject><subject>Medical sciences</subject><subject>Membrane Glycoproteins - physiology</subject><subject>Myeloblastin - immunology</subject><subject>Myeloblastin - metabolism</subject><subject>Neutrophils - enzymology</subject><subject>Neutrophils - metabolism</subject><subject>Receptors, Cell Surface - physiology</subject><subject>Transfection</subject><issn>0006-4971</issn><issn>1528-0020</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kEtPHDEMgKMKVBboP6iqXOhtIM95XJCWVWmREFzgHGUzTjfVbLKNZxD992S6K3HDF0v2Z8v-CPnK2SXnrbhaDyn1lWCsrjirmNZSNJ_IgmvRVowJdkQWbG6qruEn5BTxD2NcSaE_kxPeCKXqpl6Q54cbTrfQBzsCUpyytw4ovO4yIIYUafJ03ABdPqyW1MYx_IZIdzmNEKJFoJIWZjNtbaQRpjGn3SYMeE6OvR0QvhzyGXm-_fG0-lXdP_68Wy3vK6eZGCshW-V019YA5SPZ19p5rbnomdRKS772HUgvLW9s67gTPfde2V6runYlOnlGvu_3lov-ToCj2QZ0MAw2QprQNEzVHWt4AdUedDkhZvBml8PW5n-GMzPrNP91mlnnXNrrLGPfDvundZH0PnTwV4CLA2DR2cFnG13Ad65tWqHEzF3vOSg2XgJkgy5AdEV8BjeaPoWPL3kD362S1g</recordid><startdate>20070515</startdate><enddate>20070515</enddate><creator>von Vietinghoff, Sibylle</creator><creator>Tunnemann, Gisela</creator><creator>Eulenberg, Claudia</creator><creator>Wellner, Maren</creator><creator>Cristina Cardoso, M.</creator><creator>Luft, Friedrich C.</creator><creator>Kettritz, Ralph</creator><general>Elsevier Inc</general><general>The Americain Society of Hematology</general><scope>6I.</scope><scope>AAFTH</scope><scope>IQODW</scope><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></search><sort><creationdate>20070515</creationdate><title>NB1 mediates surface expression of the ANCA antigen proteinase 3 on human neutrophils</title><author>von Vietinghoff, Sibylle ; 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Membrane PR3 (mPR3) is expressed only on a subset of neutrophils. The aim of this study was to determine the mechanism of PR3 surface expression on human neutrophils. Neutrophils were isolated from patients and healthy controls, and hematopoietic stem cells from cord blood served as a model of neutrophil differentiation. Surface expression was analyzed by flow cytometry and confocal microscopy, and proteins were analyzed by Western blot experiments. Neutrophil subsets were separated by magnetic cell sorting. Transfection experiments were carried out in HEK293 and HL60 cell lines. Using neutrophils from healthy donors, patients with vasculitis, and neutrophilic differentiated stem cells we found that mPR3 display was restricted to cells expressing neutrophil glycoprotein NB1, a glycosylphosphatidylinositol (GPI)–linked surface receptor. mPR3 expression was decreased by enzymatic removal of GPI anchors from cell membranes and was absent in a patient with paroxysmal nocturnal hemoglobinuria. PR3 and NB1 coimmunoprecipitated from and colocalized on the neutrophil plasma membrane. Transfection with NB1 resulted in specific PR3 surface binding in different cell types. We conclude that PR3 membrane expression on neutrophils is mediated by the NB1 receptor.</abstract><cop>Washington, DC</cop><pub>Elsevier Inc</pub><pmid>17244676</pmid><doi>10.1182/blood-2006-10-055327</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Antibodies, Antineutrophil Cytoplasmic - immunology Antigens, Surface - metabolism Biological and medical sciences Cell Membrane - metabolism Cells, Cultured Fetal Blood - cytology Glycosylphosphatidylinositols - metabolism GPI-Linked Proteins Hematologic and hematopoietic diseases Hematopoietic Stem Cells - metabolism Humans Immunoprecipitation In Vitro Techniques Isoantigens - physiology Medical sciences Membrane Glycoproteins - physiology Myeloblastin - immunology Myeloblastin - metabolism Neutrophils - enzymology Neutrophils - metabolism Receptors, Cell Surface - physiology Transfection |
title | NB1 mediates surface expression of the ANCA antigen proteinase 3 on human neutrophils |
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