Bloksma N, Kubicka-Muranyi M, Schuppe H C, Gleichmann E, Gleichmann H
Research Institute of Toxicology-Immunotoxicology, Utrecht University, The Netherlands.
Crit Rev Toxicol. 1995;25(5):369-96. doi: 10.3109/10408449509049338.
This article reviews results obtained with popliteal lymph node assays (PLNAs) in rodents and discusses their ability to detect and analyze immunotoxic effects of drugs and other low molecular weight (LMW) chemicals. In its basic form, the PLNA measures activation of the draining lymph node of the hind paw (i.e., the PLN) after injection of a test chemical into the hind foot pad. The assay appears to be appropriate to recognize sensitizing, that is, allergenic and autoimmunogenic, chemicals, as well as nonsensitizing immunostimulatory chemicals. With modifications, PLNAs can detect immunosuppressive chemicals and distinguish sensitizing from nonsensitizing chemicals. Furthermore, modified PLNAs enable detection of known as well as unknown sensitizing metabolites, and may assist in the identification of the self-molecules that act as carriers for chemical sensitization or as targets of chemical-induced autoimmune disease. Experience with PLNAs shows that they are rapid, reproducible, and objective tests for recognition of sensitizing or otherwise immunomodulating chemicals. Because current protocols of toxicity testing are insensitive in predicting a chemical's potential to result in immunomodulation, PLNAs, when further validated, may provide welcome supplements to routine toxicity screening of chemicals, thus enhancing chemical safety.
本文综述了在啮齿动物中进行腘窝淋巴结试验（PLNA）所获得的结果，并讨论了其检测和分析药物及其他低分子量（LMW）化学物质免疫毒性作用的能力。PLNA的基本形式是在将受试化学物质注射到后脚垫后，测量后爪引流淋巴结（即腘窝淋巴结，PLN）的激活情况。该试验似乎适用于识别致敏性化学物质，即变应原性和自身免疫原性化学物质，以及非致敏性免疫刺激性化学物质。通过改进，PLNA可以检测免疫抑制性化学物质，并区分致敏性和非致敏性化学物质。此外，改进后的PLNA能够检测已知和未知的致敏性代谢产物，并可能有助于识别作为化学致敏载体或化学诱导自身免疫性疾病靶点的自身分子。PLNA的经验表明，它们是识别致敏性或其他免疫调节性化学物质的快速、可重复且客观的试验。由于当前的毒性测试方案在预测化学物质导致免疫调节的潜力方面不敏感，PLNA在进一步验证后，可能为化学物质的常规毒性筛查提供受欢迎的补充，从而提高化学物质的安全性。
