Isolated Human Peripheral Blood Mononuclear Cell (PBMC), a Cost Effective Tool for Predicting Immunosuppressive Effects of Drugs and Xenobiotics.

Abstract

The science of immunotoxicology began in the early 1970s, following the recognition of increased sensitivity to infection following exposure of test species, including monkeys, hamsters, ducks, rats, mice and guinea pigs to various xenobiotics. Reduced resistance to infectious disease was a well-documented consequence of primary and acquired immunodeficiencies, but a novel outcome of xenobiotic exposure, leading some to characterize xenobiotic-induced immunosuppression as “chemical AIDS”. Although the comparison was scientifically inappropriate, “immunotoxicity” was often thought of as synonymous with “immunosuppression” during the formative years of the discipline, although hypersensitivity, allergy, and autoimmunity were recognized as potential exposure outcomes. Assessment of potential adverse effects on the immune system is an important component of the overall evaluation of toxicity of personal care products, chemicals and drugs. Current public opinion and ethical considerations have stimulated efforts to reduce the number of animals used to test the toxicity of chemicals, drugs and personal care products. However, only limited effort has gone into developing in-vitro or in silico methods to detect immune dysfunction. This may be at least partially attributable to the sheer complexity of the immune response, although there has been sufficient progress to warrant continued investigation along these lines. A peripheral blood mononuclear cell (PBMC) is any blood cell having a round nucleus such as lymphocyte, monocyte or a macrophage. These blood cells are a critical component in the immune system to fight infection and adapt to intruders. These cells can be extracted from whole blood using ficoll, a hydrophilic polysaccharide that separates layers of blood, followed by gradient centrifugation, which will separate the blood into a top layer of plasma, followed by a lower layer of PBMCs and then a fraction of polymorphonuclear cells (such as neutrophils and eosinophils) and finally a bottom layer of erythrocytes. The polymorphonuclear cells can be further isolated by lysing the red blood cells. PBMCs are widely used in research and toxicology applications. Peripheral blood mononuclear cells (PBMC) give selective responses to the immune system and are the major cells in the human body immunity. They contain several types of cells such as lymphocytes,monocytes or macrophages. Because peripheral blood is the place where exposure to chemicals occurs,these fundamentally important PBMCs are prone to be influenced by drugsand chemicals. This is why the availability of PBMCs from peripheral bloodis very important for researchers studying toxicity of new drugs or drugs or drugs or chemical compounds. There are many Applications for PBMCs in toxicology research including: