间充质干细胞
脂肪组织
免疫球蛋白轻链
先天免疫系统
间质细胞
淀粉样变性
免疫系统
细胞生物学
病理
补体系统
细胞外基质
趋化因子
炎症
淀粉样蛋白(真菌学)
医学
淀粉样变性
纤维
生物
癌症研究
化学
免疫学
生物化学
抗体
植物
作者
Torri L. Jordan,Khansaa Maar,Keely R. Redhage,Pinaki Misra,Luis M. Blancas‐Mejía,Chris Dick,Jonathan S. Wall,Aaron Williams,Allan B. Dietz,André J. van Wijnen,Yi Lin,Marina Ramı́rez-Alvarado
出处
期刊:Leukemia
[Springer Nature]
日期:2019-12-03
卷期号:34 (5): 1383-1393
被引量:20
标识
DOI:10.1038/s41375-019-0640-4
摘要
Light chain (AL) amyloidosis is a progressive, degenerative disease characterized by the misfolding and amyloid deposition of immunoglobulin light chain (LC). The amyloid deposits lead to organ failure and death. Our laboratory is specifically interested in cardiac involvement of AL amyloidosis. We have previously shown that the fibrillar aggregates of LC proteins can be cytotoxic and arrest the growth of human RFP-AC16 cardiomyocytes in vitro. We showed that adipose-derived mesenchymal stromal cells (AMSC) can rescue the cardiomyocytes from the fibril-induced growth arrest through contact-dependent mechanisms. In this study, we examined the transcriptome changes of human cardiomyocytes and AMSC in the presence of AL amyloid fibrils. The presence of fibrils causes a ‘priming’ immune response in AMSC associated with interferon associated genes. Exposure to AL fibrils induced changes in the pathways associated with immune response and extracellular matrix components in cardiomyocytes. We also observed upregulation of innate immune-associated transcripts (chemokines, cytokines, and complement), suggesting that amyloid fibrils initiate an innate immune response on these cells, possibly due to phenotypic transformation. This study corroborates and expands our previous studies and identifies potential new immunologic mechanisms of action for fibril toxicity on human cardiomyocytes and AMSC rescue effect on cardiomyocytes.
科研通智能强力驱动
Strongly Powered by AbleSci AI