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Polymorphonuclear granulocytes (PMNs) and peripheral blood mononuclear cells (PBMCs) are abundant in the vicinity of CII in RA joints, and both PMN and PBMC reactivity against anti\u2010CII IC individually relate to early joint destruction and early elevation of CRP and ESR in RA. We searched for CII\u2010dependent mechanisms that might attract PMNs and PBMCs to RA joints. Human PBMCs and PMNs were stimulated with anti\u2010CII ICs and control ICs, either individually or in cocultures. Cocultured PMNs and PBMCs stimulated with anti\u2010CII ICs synergistically augmented production of the chemokines CXCL8, RANTES and MCP\u20101, whereas downregulation was seen with control IC. This upregulation was unique to chemokines, as TNF\u2010\u03b1, IL\u20101\u03b2, and GM\u2010CSF were downregulated in anti\u2010CII IC\u2010stimulated cocultures. The coculture\u2010associated chemokine upregulation depended on endogenous TLR4 ligand(s) and functionally active PMN enzymes, and was partially mediated by GM\u2010CSF. As anti\u2010CII levels peak around the time of RA diagnosis, this mechanism can attract inflammatory cells to joints in early RA and intensify the anti\u2010CII\u2010associated acute onset RA phenotype.<\/jats:p>","DOI":"10.1002\/eji.201646496","type":"journal-article","created":{"date-parts":[[2016,9,13]],"date-time":"2016-09-13T09:36:52Z","timestamp":1473759412000},"page":"2822-2834","source":"Crossref","is-referenced-by-count":6,"title":["Granulocyte\u2010augmented chemokine production induced by type II collagen containing immune complexes is mediated via TLR4 in rheumatoid arthritis patients"],"prefix":"10.1002","volume":"46","author":[{"given":"Vivek Anand","family":"Manivel","sequence":"first","affiliation":[{"name":"Department of Immunology, Genetics and Pathology Uppsala University  Uppsala Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Azita","family":"Sohrabian","sequence":"additional","affiliation":[{"name":"Department of Immunology, Genetics and Pathology Uppsala University  Uppsala Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johan","family":"R\u00f6nnelid","sequence":"additional","affiliation":[{"name":"Department of Immunology, Genetics and Pathology Uppsala University  Uppsala Sweden"},{"name":"Unit of Rheumatology Department of Medicine Karolinska Institutet  Stockholm Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2016,10,5]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(200001)43:1<155::AID-ANR20>3.0.CO;2-3"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(200008)43:8<1831::AID-ANR19>3.0.CO;2-6"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2004.033571"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1136\/jcp.32.8.826"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780391015"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/anr.1780320906"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780370707"},{"key":"e_1_2_7_9_1","first-page":"1186","article-title":"Specificity of antibodies to type II collagen in early rheumatoid arthritis","volume":"21","author":"Cook A. 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