Departamento de Bioquímica, Biología Molecular (B) e Inmunología, Facultad de Medicina, IMIB and Regional Campus of International Excellence "Campus Mare Nostrum", Universidad de Murcia, 30100 Murcia, Spain.
Unidad de Trasplante Hepático, Servicio de Aparato Digestivo, Hospital Universitario Virgen de la Arrixaca, Murcia, Spain.
J Immunol Res. 2019 Mar 24;2019:2974753. doi: 10.1155/2019/2974753. eCollection 2019.
The presumed role of the inhibitory receptor LAIR-1 (CD305) in the inflammatory response suggests that it might contribute to the pathophysiology of chronic inflammatory diseases such as liver cirrhosis. We studied the LAIR-1 expression on liver macrophages and blood monocytes related to the progression of liver cirrhosis.
The expression of LAIR-1 was analyzed by immunohistochemistry, flow cytometry, and Western blot.
We found a decreased number of macrophages expressing LAIR-1 in cirrhotic liver that could be due to a high presence of collagen, ligand of LAIR-1, in the fibrotic tissue which could downregulate its expression or interfere with the immunostaining. The expression of LAIR-1 decreased after cell differentiation, and the total content, but not the cell surface expression, increased after activation in the HL-60 human macrophage model. Blood monocytes exhibited higher LAIR-1 expression levels in cirrhotic patients, which were evident even in early clinical stages in all monocyte subsets, and greater in the "intermediate" inflammatory monocyte subpopulation. The activation of human blood monocytes did not increase its expression on the cell surface suggesting that the increase of LAIR-1 must be the result of a specific combination of stimuli present in cirrhotic patients. This represents an exclusive feature of liver cirrhosis, since blood monocytes from other chronic inflammatory pathologies showed similar or lower LAIR-1 levels compared with those of healthy controls.
These results may indicate that monocyte LAIR-1 expression is a new biomarker to early detect liver damage caused by chronic inflammation in liver cirrhosis.
抑制性受体 LAIR-1(CD305)在炎症反应中的假定作用表明,它可能有助于慢性炎症性疾病(如肝硬化)的病理生理学。我们研究了与肝硬化进展相关的肝脏巨噬细胞和血液单核细胞上的 LAIR-1 表达。
通过免疫组织化学、流式细胞术和 Western blot 分析 LAIR-1 的表达。
我们发现肝硬化肝脏中表达 LAIR-1 的巨噬细胞数量减少,这可能是由于纤维化组织中存在大量胶原,即 LAIR-1 的配体,从而下调其表达或干扰免疫染色。细胞分化后 LAIR-1 的表达减少,HL-60 人巨噬细胞模型中激活后总含量增加,但细胞表面表达不变。肝硬化患者血液单核细胞的 LAIR-1 表达水平较高,在所有单核细胞亚群的早期临床阶段均明显升高,在“中间”炎症性单核细胞亚群中更高。人血液单核细胞的激活并未增加其细胞表面的表达,这表明 LAIR-1 的增加必须是肝硬化患者中存在的特定刺激组合的结果。这代表了肝硬化的一个独特特征,因为来自其他慢性炎症性疾病的血液单核细胞与健康对照组相比表现出相似或更低的 LAIR-1 水平。
这些结果可能表明单核细胞 LAIR-1 表达是一种新的生物标志物,可早期检测肝硬化中由慢性炎症引起的肝损伤。