Anti-class a scavenger receptor autoantibodies from systemic lupus erythematosus patients impair phagocytic clearance of apoptotic cells by macrophages in vitro.
Anti-class a scavenger receptor autoantibodies from systemic lupus erythematosus patients impair phagocytic clearance of apoptotic cells by macrophages in vitro.
复制标题
系统性红斑狼疮患者的抗a类清道夫受体自身抗体在体外损害巨噬细胞对凋亡细胞的吞噬清除
DOI：
10.1186/ar3230
复制
发表时间：
2011-01-31
影响因子：
4.9
通讯作者：
Yang CD
中科院分区：
文献类型：
--
作者：
Chen XW;Shen Y;Sun CY;Wu FX;Chen Y;Yang CD
巨噬细胞对凋亡细胞清除不足是自身耐受性破坏的原因之一。A类清道夫受体，即巨噬细胞胶原结构受体（MARCO）和清道夫受体A（SR - A），在巨噬细胞上表达，在凋亡细胞的摄取中起重要作用。先前的一项研究报道了在易患狼疮的小鼠和系统性红斑狼疮（SLE）患者中存在抗MARCO抗体。本研究的目的是调查抗A类清道夫受体抗体在各种自身免疫性疾病，特别是SLE患者中的患病率，以及这些自身抗体在巨噬细胞对凋亡细胞吞噬清除中的功能影响。
纯化的重组清道夫受体富含半胱氨酸（SRCR）多肽（MARCO的配体结合域）和重组SR - A被用作抗原。通过酶联免疫吸附测定，在未经治疗的SLE患者（n = 65）、类风湿关节炎患者（n = 65）、原发性干燥综合征患者（n = 25）和健康献血者（n = 85）的血清中检测抗SRCR和抗SR - A抗体。通过流式细胞术测定从SLE患者或健康对照中纯化的IgG对巨噬细胞吞噬凋亡细胞的影响。
抗SRCR抗体存在于SLE患者（18.5%）和类风湿关节炎患者（3.1%）中，但在原发性干燥综合征患者中不存在。抗SR - A抗体存在于SLE患者（33.8%）、类风湿关节炎患者（13.8%）和原发性干燥综合征患者（12.0%）中。来自抗SRCR或抗SR - A抗体阳性的SLE患者的IgG对凋亡细胞与巨噬细胞结合的抑制率高于来自健康对照的IgG（两者均P < 0.05）。来自抗SRCR和抗SR - A抗体均阳性的SLE患者的IgG对巨噬细胞摄取凋亡细胞的抑制率显著高于来自健康对照的IgG（P < 0.05）。
我们的结果表明，针对A类清道夫受体的自身抗体可能通过损害凋亡碎片的清除而导致自身耐受性破坏，并在自身免疫性疾病，特别是SLE的发病机制中起作用。
Introduction
Inadequate clearance of apoptotic cells by macrophages is one of the reasons for the breakdown of self-tolerance. Class A scavenger receptors, macrophage receptor with collagenous structure (MARCO) and scavenger receptor A (SR-A), which are expressed on macrophages, play important roles in the uptake of apoptotic cells. A previous study reported the presence of the anti-MARCO antibody in lupus-prone mice and systemic lupus erythematosus (SLE) patients. The purpose of this study was to investigate the prevalence of anti-class A scavenger receptor antibodies in patients with various autoimmune diseases, in particular SLE, and the functional implication of those autoantibodies in the phagocytic clearance of apoptotic cells by macrophages.
Methods
Purified recombinant scavenger receptor cysteine-rich (SRCR) polypeptide (ligand-binding domain of MARCO) and recombinant SR-A were used as antigens. By using enzyme-linked immunosorbent assay, the anti-SRCR and anti-SR-A antibodies were detected in the sera of untreated patients with SLE (n = 65), rheumatoid arthritis (n = 65), primary Sjögren syndrome (n = 25), and healthy blood donors (n = 85). The effect of IgG purified from SLE patients or healthy controls on the phagocytosis of apoptotic cells by macrophages was measured by the flow cytometry assay.
Results
Anti-SRCR antibodies were present in patients with SLE (18.5%) and rheumatoid arthritis (3.1%), but not in those with primary Sjögren syndrome. Anti-SR-A antibodies were present in patients with SLE (33.8%), rheumatoid arthritis (13.8%), and primary Sjögren syndrome (12.0%). IgG from SLE patients positive for anti-SRCR or anti-SR-A antibodies showed a higher inhibition rate on binding of apoptotic cells to macrophages than IgG from healthy controls (both P 0.05). IgG from SLE patients positive for both anti-SRCR and anti-SR-A antibodies showed a significantly higher inhibition rate on ingestion of apoptotic by macrophages than IgG from healthy controls (P 0.05).
Conclusions
Our results indicated that autoantibodies to class A scavenger receptors might contribute to the breakdown of self-tolerance by impairing the clearance of apoptotic debris and play a role in the pathogenesis of autoimmune disease, especially in SLE.
登录
查看更多内容
影响因子：
2.3
作者：
Cohen, PL;Caricchio, R
通讯作者：
Caricchio, R
DOI：
10.1084/jem.20070600
发表时间：
2007-10-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Wermeling F;Chen Y;Pikkarainen T;Scheynius A;Winqvist O;Izui S;Ravetch JV;Tryggvason K;Karlsson MC
通讯作者：
Karlsson MC
影响因子：
27.4
作者：
Tas, SW;Quartier, P;Fossati-Jimack, L
通讯作者：
Fossati-Jimack, L
影响因子：
158.5
作者：
Arbuckle, MR;McClain, MT;Harley, JB
通讯作者：
Harley, JB
影响因子：
4.8
作者：
Ojala, Juha R. M.;Pikkarainen, Timo;Tryggvason, Karl
通讯作者：
Tryggvason, Karl