Both autoimmune disease prevalence and exposure to immunotoxic chemicals have increased the last decades. As a first screening of immunotoxic chemicals possibly affecting development of autoimmunity through attenuated macrophage function, we demonstrate a promising model measuring macrophage function in isolated peritoneal macrophages (PCM) from Wistar rats and C57Bl/6 mice. Immunotoxic effects of bisphenol A (BPA) and a selection of perfluoroalkyl acids (PFAAs) were analysed in vitro assessing phagocytic function of macrophages from different sources. Phagocytosis was reduced in PCM of C57Bl/6 mice and Wistar rats after BPA and perfluoroundecanoic acid (PFUnDA) exposure, but not in macrophages derived from human and rat monocyte derived macrophages (MDM). On the other hand, in vitro exposure to mixtures of persistent organic pollutants (POPs) showed similar reductions in rat PCM and rat and human MDM phagocytosis. Reduced phagocytosis was partly due to cytotoxicity. PCM isolated from non-obese diabetic (NOD) mice, interleukin 1α/β knockout (IL-1KO) mice and new-born rats were less sensitive to the xenobiotics than PCM from adult wild type rodents. Finally, in vivo studies with NOD mice verified that POP exposure also decreased the number of pancreatic macrophages in pancreatic islets, reflecting early signs of autoimmunity development, similarly as previously described for BPA.

在过去的几十年中，自身免疫性疾病的患病率和接触免疫毒性化学物质的人数均增加了。作为可能通过减弱的巨噬细胞功能影响自身免疫发展的免疫毒性化学物质的首次筛选，我们证明了测量来自Wistar大鼠和C57Bl / 6小鼠的孤立腹膜巨噬细胞（PCM）中巨噬细胞功能的有前途的模型。在体外分析双酚A（BPA）和全氟烷基酸（PFAAs）的免疫毒性作用，以评估来自不同来源的巨噬细胞的吞噬功能。暴露于BPA和全氟十一烷酸（PFUnDA）后，C57Bl / 6小鼠和Wistar大鼠的PCM中的吞噬作用降低，但源自人和大鼠单核细胞的巨噬细胞（MDM）的巨噬细胞却没有降低。另一方面，在体外暴露于持久性有机污染物（POPs）的混合物中，大鼠PCM以及大鼠和人类MDM吞噬作用均表现出相似的降低。吞噬作用降低部分归因于细胞毒性。与成年野生型啮齿动物相比，从非肥胖糖尿病（NOD）小鼠，白介素1α/β基因敲除（IL-1KO）小鼠和新生大鼠中分离出的PCM对异源生物的敏感性要低。最后，对NOD小鼠的体内研究证实，POP暴露也减少了胰岛中胰腺巨噬细胞的数量，反映出自身免疫发展的早期迹象，与先前针对BPA的描述类似。