Hill Dwayne A, Reese Carroll T, Clarke Dwane, Martin Tanika V
Department of Biology, School of Computer, Mathematical and Natural Sciences, Morgan State University, Baltimore, Maryland 21251, USA.
Int J Environ Res Public Health. 2006 Mar;3(1):23-30. doi: 10.3390/ijerph2006030003.
Progenitor cells (PC) are the precursors for many developmental structures and are sensitive to a variety of toxic agents including the environmental contaminants, polychlorinated biphenyls (PCBs). The mechanism(s) that contributes to the development of PCB-induced progenitor cell-related fetotoxicities are not completely understood. However, several studies have demonstrated an important role for neutrophils (polymorphonucleocytes) in the development of PCB induced toxicities. Our recent findings have indicated that conditioned medium collected from PC (CMPC) exposed to a single dose of the PCB mixture, Aroclor 1248, can activate isolated neutrophil populations. Because of our recent findings, this study was conducted to determine if conditioned medium from PC treated with a PCB mixture causes neutrophils to injure PC in culture. Isolated PC were cultured and treated with different concentrations of Aroclor 1248 for 24 hours. The resulting PC-derived conditioned media was collected and its affect on neutrophil activity was analyzed. Conditioned medium from PC treated with Aroclor 1248 was chemotactic for neutrophils. The conditioned medium from Aroclor 1248 treated- PC also stimulated neutrophils to release super oxide anion, cathepsin G and elastase into culture medium. Furthermore, the conditioned medium from Aroclor 1248 treated- PC was able to stimulate neutrophils to cause progenitor cell toxicity in co-cultures. The conditioned medium from Aroclor 1248 treated-PC was not toxic to individual neutrophil cultures or PC cultures. Moreover, the addition of a protease inhibitor to the co-cultures containing neutrophils and PC, afforded protection against neutrophil-induced cytotoxicity of PC. These data suggest that a PCB mixture can cause progenitor cells to produce a factor(s) that activates neutrophils and stimulates them to damage PC populations in culture.
祖细胞（PC）是许多发育结构的前体，并且对包括环境污染物多氯联苯（PCB）在内的多种有毒物质敏感。导致PCB诱导的与祖细胞相关的胎儿毒性发展的机制尚未完全明了。然而，多项研究已证明中性粒细胞（多形核细胞）在PCB诱导的毒性发展中起重要作用。我们最近的研究结果表明，从暴露于单剂量PCB混合物Aroclor 1248的PC收集的条件培养基（CMPC）可激活分离的中性粒细胞群体。基于我们最近的研究结果，进行了本研究以确定用PCB混合物处理的PC的条件培养基是否会导致中性粒细胞在培养中损伤PC。分离的PC进行培养并用不同浓度的Aroclor 1248处理24小时。收集所得的源自PC的条件培养基并分析其对中性粒细胞活性的影响。用Aroclor 1248处理的PC的条件培养基对中性粒细胞具有趋化作用。用Aroclor 1248处理的PC的条件培养基还刺激中性粒细胞向培养基中释放超氧阴离子、组织蛋白酶G和弹性蛋白酶。此外，用Aroclor 1248处理的PC的条件培养基能够刺激中性粒细胞在共培养中导致祖细胞毒性。用Aroclor 1248处理的PC的条件培养基对单个中性粒细胞培养物或PC培养物无毒。此外，向含有中性粒细胞和PC的共培养物中添加蛋白酶抑制剂可提供针对中性粒细胞诱导的PC细胞毒性的保护作用。这些数据表明，PCB混合物可导致祖细胞产生一种因子，该因子激活中性粒细胞并刺激它们在培养中损伤PC群体。
