{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T12:15:22Z","timestamp":1791288922512,"version":"4.3.0"},"reference-count":41,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2007,5,25]],"date-time":"2007-05-25T00:00:00Z","timestamp":1180051200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2007,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>The tumor necrosis factor (TNF) family member B lymphocyte stimulator (BLyS) is an important regulator of B cell\u2013dependent autoimmunity. Similar to other TNF family members, it is generally expressed as a transmembrane protein and cleaved from the surface to release its active soluble form. This study was undertaken to investigate the expression of BLyS and regulation of BLyS release from the surface of neutrophils infiltrating the rheumatoid joint.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>BLyS expression was studied in neutrophils from the synovial fluid and peripheral blood of patients with rheumatoid arthritis (RA) and healthy controls, by flow cytometry, Western blotting, and immunofluorescence analyses. Peripheral blood neutrophils cultured with 50% RA synovial fluid were study for membrane expression of BLyS. Neutrophils were exposed to a range of proinflammatory cytokines to study the mechanisms of surface loss of BLyS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Expression of BLyS was detected on the surface of peripheral blood neutrophils from both RA patients and healthy controls, whereas BLyS expression on synovial fluid neutrophils was very low. Constitutive expression of BLyS was observed in neutrophils, both on the cell membrane and in intracellular stores; however, BLyS release from each of these sites was found to be regulated independently. Of the various cytokine stimuli, only TNF\u03b1 triggered release of BLyS from the neutrophil membrane. This process led to release of physiologically relevant quantities of soluble BLyS, which was dependent on the presence of the pro\u2010protein convertase furin. In contrast, stimulation of neutrophils with granulocyte colony\u2010stimulating factor induced BLyS release from the intracellular stores. Incubation of peripheral blood neutrophils with RA synovial fluid led to TNF\u03b1\u2010dependent shedding of BLyS from the cell surface.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These findings indicate that as neutrophils enter the site of inflammation, they release surface\u2010expressed BLyS in a TNF\u03b1\u2010dependent manner, and thus may contribute to local stimulation of autoimmune B cell responses.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.22697","type":"journal-article","created":{"date-parts":[[2007,5,28]],"date-time":"2007-05-28T06:53:16Z","timestamp":1180335196000},"page":"1776-1786","source":"Crossref","is-referenced-by-count":78,"title":["Tumor necrosis factor \u03b1 activates release of B lymphocyte stimulator by neutrophils infiltrating the rheumatoid joint"],"prefix":"10.1002","volume":"56","author":[{"given":"Lakhvir K.","family":"Assi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"See Heng","family":"Wong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Ludwig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karim","family":"Raza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Gordon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Salmon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janet M.","family":"Lord","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dagmar","family":"Scheel\u2010Toellner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2007,5,25]]},"reference":[{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0889-857X(21)00463-4"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20052371"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.167.3.1601"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2567.2006.02424.x"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20021343"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2005.035691"},{"key":"e_1_2_7_8_2","first-page":"231","article-title":"Predictive value of antibodies to cyclic citrullinated peptide in patients with very early inflammatory arthritis","volume":"32","author":"Raza K","year":"2005","journal-title":"J Rheumatol"},{"key":"e_1_2_7_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/jlb.65.5.680"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.23.15978"},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.285.5425.260"},{"key":"e_1_2_7_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/35010115"},{"key":"e_1_2_7_13_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.189.11.1747"},{"key":"e_1_2_7_14_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI0214121"},{"key":"e_1_2_7_15_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.166.1.6"},{"key":"e_1_2_7_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(200106)44:6<1313::AID-ART223>3.0.CO;2-S"},{"key":"e_1_2_7_17_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.11.6261"},{"key":"e_1_2_7_18_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj3270625"},{"key":"e_1_2_7_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780310302"},{"key":"e_1_2_7_20_2","doi-asserted-by":"crossref","first-page":"3447","DOI":"10.4049\/jimmunol.136.9.3447","article-title":"Metabolic comparison between basophils and other leukocytes from human blood","volume":"136","author":"De Boer M","year":"1986","journal-title":"J Immunol"},{"key":"e_1_2_7_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/370555a0"},{"key":"e_1_2_7_22_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-02-0564"},{"key":"e_1_2_7_23_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-12-3775"},{"key":"e_1_2_7_24_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.131.3.775"},{"key":"e_1_2_7_25_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.165.6.3366"},{"key":"e_1_2_7_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm934"},{"key":"e_1_2_7_27_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.2004.02563.x"},{"key":"e_1_2_7_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri1838"},{"key":"e_1_2_7_29_2","doi-asserted-by":"publisher","DOI":"10.1186\/ar1733"},{"key":"e_1_2_7_30_2","first-page":"464","article-title":"Belimumab Human Genome Sciences\/Cambridge Antibody Technology\/GlaxoSmithKline","volume":"7","author":"Ding C","year":"2006","journal-title":"Curr Opin Investig Drugs"},{"key":"e_1_2_7_31_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.21650"},{"key":"e_1_2_7_32_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI25265"},{"key":"e_1_2_7_33_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.10860"},{"key":"e_1_2_7_34_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V97.1.198"},{"key":"e_1_2_7_35_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.190.11.1697"},{"key":"e_1_2_7_36_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.7.3370"},{"key":"e_1_2_7_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1471-4906(01)02159-7"},{"key":"e_1_2_7_38_2","doi-asserted-by":"publisher","DOI":"10.1186\/ar1855"},{"key":"e_1_2_7_39_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/20.9.2191"},{"key":"e_1_2_7_40_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.21.10277"},{"key":"e_1_2_7_41_2","doi-asserted-by":"publisher","DOI":"10.1177\/002215540405200502"},{"key":"e_1_2_7_42_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1994.tb06231.x"}],"container-title":["Arthritis &amp; Rheumatism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fart.22697","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.22697","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T18:31:23Z","timestamp":1697049083000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/art.22697"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,5,25]]},"references-count":41,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2007,6]]}},"alternative-id":["10.1002\/art.22697"],"URL":"https:\/\/doi.org\/10.1002\/art.22697","archive":["Portico"],"relation":{},"ISSN":["0004-3591","1529-0131"],"issn-type":[{"value":"0004-3591","type":"print"},{"value":"1529-0131","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,5,25]]}}}