Department of Anesthesiology and Intensive Care Medicine, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany.
Anesthesia, Intensive Care and Pain Management, South Egypt Cancer Institute, Assiut University, Assiut 7111, Egypt.
Cells. 2023 Jul 17;12(14):1873. doi: 10.3390/cells12141873.
CD45 is a transmembrane glycoprotein that is located on the surface of all leukocytes and modulates both innate and adaptive immune system functions. In a recent study, inflammation modulated the CD45 expression in leukocytes, but the effect on the expression of CD45 subtypes is unknown. In the present study, we therefore investigated the effect of inflammatory conditions in humans (surgery, sepsis) and ex vivo incubation with lipopolysaccharides (LPS) on the expression of the subtypes CD45RA and CD45RO in granulocytes, lymphocytes, and monocytes. Whole blood samples were obtained from healthy volunteers, postoperative patients, and patients with sepsis at day 1 of diagnosis, respectively. Samples were incubated with fluorescent antibodies directed against CD45, CD45RA and CD45RO in the absence and presence of lipopolysaccharide and subjected to flow cytometry. In comparison to volunteers, CD45RA surface expression in postoperative and septic patients was reduced by 89% exclusively on granulocytes, but not on lymphocytes or monocytes. In contrast, CD45RO was exclusively reduced on lymphocytes, by 82%, but not on other cell types. Receiver operating characteristic curve analyses demonstrated that CD45RA (on granulocytes) and CD45RO (on lymphocytes) allow a good differentiation of volunteers and patients with sepsis (AUC = 0.9; = 0.0001). The addition of LPS to the whole blood samples obtained from volunteers, postoperative patients, and septic patients markedly increased the CD45RO expression in granulocytes, lymphocytes, and monocytes. In contrast, LPS reduced CD45RA exclusively on monocytes. In conclusion, the surface expression of CD45RA and CD45RO is regulated in inflammation in a cell-type- and stimulus-specific manner. Considering that CD45 subtypes are critically involved in immune system signaling, the pathophysiologic and diagnostic implications warrant further investigation.
CD45 是一种跨膜糖蛋白，位于所有白细胞的表面，调节固有和适应性免疫系统的功能。在最近的一项研究中，炎症调节了白细胞中的 CD45 表达，但对 CD45 亚型表达的影响尚不清楚。在本研究中，我们因此研究了炎症条件（手术、败血症）对人类白细胞中 CD45RA 和 CD45RO 亚型表达的影响，以及体外孵育脂多糖（LPS）对粒细胞、淋巴细胞和单核细胞中这些亚型表达的影响。从健康志愿者、术后患者和诊断为败血症的患者中分别获得全血样本。将样本与针对 CD45、CD45RA 和 CD45RO 的荧光抗体在不存在和存在脂多糖的情况下孵育，并进行流式细胞术分析。与志愿者相比，术后和败血症患者的 CD45RA 表面表达在粒细胞上降低了 89%，但在淋巴细胞和单核细胞上没有降低。相比之下，CD45RO 仅在淋巴细胞上降低了 82%，而在其他细胞类型上没有降低。受试者工作特征曲线分析表明，CD45RA（在粒细胞上）和 CD45RO（在淋巴细胞上）可以很好地区分志愿者和败血症患者（AUC=0.9；P=0.0001）。将 LPS 添加到从志愿者、术后患者和败血症患者获得的全血样本中，明显增加了粒细胞、淋巴细胞和单核细胞中的 CD45RO 表达。相反，LPS 仅降低单核细胞上的 CD45RA。总之，CD45RA 和 CD45RO 的表面表达在炎症中以细胞类型和刺激特异性的方式受到调节。鉴于 CD45 亚型在免疫系统信号转导中起着至关重要的作用，其病理生理和诊断意义值得进一步研究。
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