Frenkel O, Shani E, Ben-Bassat I, Brok-Simoni F, Rozenfeld-Granot G, Kajakaro G, Rechavi G, Amariglio N, Shinar E, Danon D
Department of Haematology, Chaim Sheba Medical Centre, Tel-Hashomer, Israel.
Clin Exp Immunol. 2002 Apr;128(1):59-66. doi: 10.1046/j.1365-2249.2002.01630.x.
Macrophages play a major role in almost all stages of the complex process of wound healing. It has been previously shown that the incorporation of a hypo-osmotic shock step, in the process of monocyte-concentrate preparation from a blood unit, induces monocyte/macrophage activation. As the macrophages are produced using a unique, closed and sterile system, they are suitable for local application on ulcers in elderly and paraplegic patients. Enhanced phagocytosis by the activated cells, as well as increased secretion of cytokines such as IL-1, IL-6, were detected in a recent study which are in accord with the very encouraging clinical results. In the present study, we used DNA microarrays to analyse the differential gene expressions of the hypo-osmotic shock-activated monocytes/macrophages and compare them to non-treated cells. Of the genes that exhibited differences of expression in the activated cell population, 94% (68/72) displayed increased activity. The mRNA levels of 43/68 of these genes (63%) were found to be 1.5-fold or higher (1.5-7.98) in the activated macrophages cell population as compared to the non-treated cells. Only four genes were found to have lower mRNA levels in the activated cells, with ratios of expression of 0.62-0.8, which may suggest that the changes are insignificant. A significant number of the genes that showed increased levels of expression is known to be directly involved in macrophage function and wound healing. This may correlate with the increased secretion of different cytokines by the activated macrophages depicted previously. Other groups of genes expressed are known to be involved in important pathways such as neuronal growth and function, developmental defects and cancer. The hypo-osmotic shock induces a gene expression profile of cytokines and receptors in the activated cells. These may evoke potential abilities to produce a variety of protein products needed in the wound healing process and may bring to light possibilities for other therapeutic applications of these cells.
巨噬细胞在伤口愈合这一复杂过程的几乎所有阶段都发挥着主要作用。先前已有研究表明，在从血液单位制备单核细胞浓缩物的过程中加入低渗休克步骤，可诱导单核细胞/巨噬细胞活化。由于巨噬细胞是使用独特、封闭且无菌的系统产生的，它们适用于局部应用于老年和截瘫患者的溃疡。最近一项研究检测到活化细胞的吞噬作用增强，以及白细胞介素 -1、白细胞介素 -6 等细胞因子的分泌增加，这与非常令人鼓舞的临床结果相符。在本研究中，我们使用 DNA 微阵列分析低渗休克激活的单核细胞/巨噬细胞的差异基因表达，并将它们与未处理的细胞进行比较。在活化细胞群体中表现出表达差异的基因中，94%（68/72）显示活性增加。与未处理的细胞相比，这些基因中的 43/68（63%）的 mRNA 水平在活化的巨噬细胞群体中为 1.5 倍或更高（1.5 - 7.98）。仅发现四个基因在活化细胞中的 mRNA 水平较低，表达比率为 0.62 - 0.8，这可能表明这些变化不显著。大量表达水平增加的基因已知直接参与巨噬细胞功能和伤口愈合。这可能与先前描述的活化巨噬细胞分泌不同细胞因子的增加相关。其他表达的基因组已知参与重要途径，如神经元生长和功能、发育缺陷和癌症。低渗休克在活化细胞中诱导细胞因子和受体的基因表达谱。这些可能引发产生伤口愈合过程中所需的各种蛋白质产物的潜在能力，并可能揭示这些细胞其他治疗应用的可能性。
