Granulocyte-augmented chemokine production induced by type II collagen containing immune complexes is mediated via TLR4 in rheumatoid arthritis patients.
Granulocyte-augmented chemokine production induced by type II collagen containing immune complexes is mediated via TLR4 in rheumatoid arthritis patients.
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DOI：
10.1002/eji.201646496
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发表时间：
2016-12
影响因子：
5.4
通讯作者：
Ronnelid, Johan
中科院分区：
文献类型：
--
作者：
Manivel, Vivek Anand;Sohrabian, Azita;Ronnelid, Johan
关键词：
早期抗II型胶原抗体升高的类风湿关节炎(RA)患者具有明显的急性起病表型，与表面结合的抗CII免疫复合物(ICs)诱导的细胞因子、高C反应蛋白(CRP)和红细胞沉降率(ESR)有关。RA关节CII附近有大量的中性粒细胞(PMN)和外周血单核细胞(PBMC)，PMN和PBMC对抗CII IC的反应性分别与RA关节早期破坏和CRP、ESR的早期升高有关。我们寻找可能吸引PMN和PBMCs到RA关节的CII依赖机制。人外周血单个核细胞(PBMC)和中性粒细胞(PMN)分别用抗CIIIC和对照ICs单独或在共培养条件下刺激。共培养的PMN和PBMC经抗CII IC刺激后，趋化因子CXCL8、RANTES和MCP-1的产生协同增加，而对照IC则下调。这种上调是趋化因子所特有的，因为在抗CIIIC刺激的共培养中，肿瘤坏死因子-α、IL-1β和GM-CSF的表达下调。共培养相关趋化因子的上调依赖于内源性TLR4L(S)和功能活性的PMN酶，并部分由GM-CSF介导。由于抗CII抗体水平在RA诊断前后达到峰值，这一机制可吸引炎性细胞进入早期RA关节，增强抗CII抗体相关的急性发作RA的表型。
Rheumatoid arthritis (RA) patients with early elevations of antibodies against collagen type II (CII) have a distinct acute onset phenotype, associated with cytokine induction by surface‐bound anti‐CII‐containing immune complexes (ICs) and high C‐reactive protein (CRP) and erythrocyte sedimentation rate (ESR). 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‐CII IC individually relate to early joint destruction and early elevation of CRP and ESR in RA. We searched for CII‐dependent mechanisms that might attract PMNs and PBMCs to RA joints. Human PBMCs and PMNs were stimulated with anti‐CII ICs and control ICs, either individually or in cocultures. Cocultured PMNs and PBMCs stimulated with anti‐CII ICs synergistically augmented production of the chemokines CXCL8, RANTES and MCP‐1, whereas downregulation was seen with control IC. This upregulation was unique to chemokines, as TNF‐α, IL‐1β, and GM‐CSF were downregulated in anti‐CII IC‐stimulated cocultures. The coculture‐associated chemokine upregulation depended on endogenous TLR4 ligand(s) and functionally active PMN enzymes, and was partially mediated by GM‐CSF. As anti‐CII levels peak around the time of RA diagnosis, this mechanism can attract inflammatory cells to joints in early RA and intensify the anti‐CII‐associated acute onset RA phenotype.
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影响因子：
--
作者：
Mullazehi, Mohammed;Mathsson, Linda;Ronnelid, Johan
通讯作者：
Ronnelid, Johan
影响因子：
4.9
作者：
Mullazehi M;Wick MC;Klareskog L;van Vollenhoven R;Rönnelid J
通讯作者：
Rönnelid J
影响因子：
6.7
作者：
Rittirsch D;Flierl MA;Day DE;Nadeau BA;Zetoune FS;Sarma JV;Werner CM;Wanner GA;Simmen HP;Huber-Lang MS;Ward PA
通讯作者：
Ward PA
影响因子：
3.5
作者：
Devaney, JM;Greene, CM;McElvaney, NG
通讯作者：
McElvaney, NG
影响因子：
--
作者：
Ospelt, Caroline;Brentano, Fabia;Kyburz, Diego
通讯作者：
Kyburz, Diego