Division of Pulmonary Medicine, Department of Biochemistry and Molecular Biology, Mayo Clinic Arizona, Scottsdale, AZ, USA.
J Allergy Clin Immunol. 2012 Sep;130(3):572-84. doi: 10.1016/j.jaci.2012.07.025.
The respective life histories of human subjects and mice are well defined and describe a unique story of evolutionary conservation extending from sequence identity within the genome to the underpinnings of biochemical, cellular, and physiologic pathways. As a consequence, the hematopoietic lineages of both species are invariantly maintained, each with identifiable eosinophils. This canonical presence nonetheless does not preclude disparities between human and mouse eosinophils, their effector functions, or both. Indeed, many books and reviews dogmatically highlight differences, providing a rationale to discount the use of mouse models of human eosinophilic diseases. We suggest that this perspective is parochial and ignores the wealth of available studies and the consensus of the literature that overwhelming similarities (and not differences) exist between human and mouse eosinophils. The goal of this review is to summarize this literature and in some cases provide experimental details comparing and contrasting eosinophils and eosinophil effector functions in human subjects versus mice. In particular, our review will provide a summation and an easy-to-use reference guide to important studies demonstrating that although differences exist, more often than not, their consequences are unknown and do not necessarily reflect inherent disparities in eosinophil function but instead species-specific variations. The conclusion from this overview is that despite nominal differences, the vast similarities between human and mouse eosinophils provide important insights as to their roles in health and disease and, in turn, demonstrate the unique utility of mouse-based studies with an expectation of valid extrapolation to the understanding and treatment of patients.
人类和小鼠的各自生命史都有明确的定义,描述了一个独特的进化保守故事,从基因组内的序列同一性延伸到生化、细胞和生理途径的基础。因此,两种物种的造血谱系都不变地维持着,每种谱系都有可识别的嗜酸性粒细胞。这种典型的存在并不能排除人类和小鼠嗜酸性粒细胞之间的差异、它们的效应功能或两者兼而有之。事实上,许多书籍和评论都教条地强调了差异,为否定使用小鼠模型来研究人类嗜酸性粒细胞疾病提供了依据。我们认为,这种观点是狭隘的,忽略了大量现有的研究和文献共识,即人类和小鼠嗜酸性粒细胞之间存在压倒性的相似之处(而不是差异)。本综述的目的是总结这些文献,并在某些情况下提供实验细节,比较和对比人类和小鼠嗜酸性粒细胞及其效应功能。特别是,我们的综述将提供一个总结和一个易于使用的参考指南,展示了重要的研究,尽管存在差异,但它们的后果往往是未知的,并不一定反映了嗜酸性粒细胞功能的内在差异,而是反映了物种特异性的变异。从这个综述中得出的结论是,尽管存在名义上的差异,但人类和小鼠嗜酸性粒细胞之间的巨大相似性为它们在健康和疾病中的作用提供了重要的见解,并反过来证明了基于小鼠的研究的独特效用,期望能够将其有效外推到对患者的理解和治疗上。