Decay-Accelerating Factor Differentially Associates With Complement-Mediated Damage in Synovium After Meniscus Tear as Compared to Anterior Cruciate Ligament Injury.

IF 4.3 4区 医学 Q2 IMMUNOLOGY Immune Network Pub Date : 2024-04-29 eCollection Date: 2024-04-01 DOI:10.4110/in.2024.24.e17
V Michael Holers, Rachel M Frank, Michael Zuscik, Carson Keeter, Robert I Scheinman, Christopher Striebich, Dmitri Simberg, Michael R Clay, Larry W Moreland, Nirmal K Banda
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Abstract

We have reported that anterior cruciate ligament (ACL) injury leads to the differential dysregulation of the complement system in the synovium as compared to meniscus tear (MT) and proposed this as a mechanism for a greater post-injury prevalence of post traumatic osteoarthritis (PTOA). To explore additional roles of complement proteins and regulators, we determined the presence of decay-accelerating factor (DAF), C5b, and membrane attack complexes (MACs, C5b-9) in discarded surgical synovial tissue (DSST) collected during arthroscopic ACL reconstructive surgery, MT-related meniscectomy, osteoarthritis (OA)-related knee replacement surgery and normal controls. Multiplexed immunohistochemistry was used to detect and quantify complement proteins. To explore the involvement of body mass index (BMI), after these 2 injuries, we examined correlations among DAF, C5b, MAC and BMI. Using these approaches, we found that synovial cells after ACL injury expressed a significantly lower level of DAF as compared to MT (p<0.049). In contrast, C5b staining synovial cells were significantly higher after ACL injury (p<0.0009) and in OA DSST (p<0.039) compared to MT. Interestingly, there were significantly positive correlations between DAF & C5b (r=0.75, p<0.018) and DAF & C5b (r=0.64 p<0.022) after ACL injury and MT, respectively. The data support that DAF, which should normally dampen C5b deposition due to its regulatory activities on C3/C5 convertases, does not appear to exhibit that function in inflamed synovia following either ACL injury or MT. Ineffective DAF regulation may be an additional mechanism by which relatively uncontrolled complement activation damages tissue in these injury states.

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与前十字韧带损伤相比,半月板撕裂后衰变加速因子与补体介导的滑膜损伤有不同的关联。
我们曾报道过,与半月板撕裂(MT)相比,前交叉韧带(ACL)损伤会导致滑膜中的补体系统出现不同程度的失调,并提出这是损伤后创伤后骨关节炎(PTOA)发病率较高的一个机制。为了探索补体蛋白和调节因子的其他作用,我们测定了在关节镜前交叉韧带重建手术、MT相关半月板切除术、骨关节炎(OA)相关膝关节置换手术和正常对照组中收集的废弃手术滑膜组织(DSST)中存在的衰变加速因子(DAF)、C5b和膜攻击复合物(MACs,C5b-9)。多重免疫组化技术用于检测和量化补体蛋白。为了探索体重指数(BMI)对这两种损伤的影响,我们研究了 DAF、C5b、MAC 和 BMI 之间的相关性。通过这些方法,我们发现前交叉韧带损伤后滑膜细胞表达的 DAF 水平明显低于 MT(p
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来源期刊
Immune Network
Immune Network Immunology and Microbiology-Immunology
CiteScore
2.90
自引率
3.30%
发文量
36
期刊介绍: Immune Network publishes novel findings in basic and clinical immunology and aims to provide a medium through which researchers in various fields of immunology can share and connect. The journal focuses on advances and insights into the regulation of the immune system and the immunological mechanisms of various diseases. Research that provides integrated insights into translational immunology is given preference for publication. All submissions are evaluated based on originality, quality, clarity, and brevity
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