Donovan Kathleen M, Leidinger Mariah R, McQuillen Logan P, Goeken J Adam, Hogan Christine M, Harwani Sailesh C, Flaherty Heather A, Meyerholz David K
Office of Animal Resources, University of Iowa, Iowa City, Iowa, USA.
Departments of Pathology, University of Iowa, Iowa City, Iowa, USA.
Comp Med. 2018 Oct 1;68(5):341-348. doi: 10.30802/AALAS-CM-18-000017. Epub 2018 Sep 18.
Allograft inflammatory factor 1 (AIF1) is a commonly used marker for microglia in the brains of humans and some animal models but has had limited applications elsewhere. We sought to determine whether AIF1 can be used as a macrophage marker across common laboratory animal species and tissues. We studied tissues (that is, spleen, liver, and lung) with defined macrophage populations by using an AIF1 immunostaining technique previously validated in human tissue. Tissues were collected from various mouse strains ( = 20), rat strains ( = 15), pigs ( = 4), ferrets ( = 4), and humans ( = 4, lung only). All samples of liver had scattered immunostaining in interstitial cells, consistent with resident tissue macrophages (Kupffer cells). Spleen samples had cellular immunostaining of macrophages in both the red and white pulp compartments, but the red pulp had more immunostained cellular aggregates and, in some species, increased immunostaining intensity compared with white pulp. In lung, alveolar macrophages had weak to moderate staining, whereas interstitial and perivascular macrophages demonstrated moderate to robust staining. Incidental lesions and tissue changes were detected in some sections, including a tumor, inducible bronchus-associated lymphoid tissue, and inflammatory lesions that demonstrated AIF1 immunostaining of macrophages. Finally, we compared AIF1 immunostaining of alveolar macrophages between a hypertensive rat model (SHR strain) and a normotensive model (WKY strain). SHR lungs had altered intensity and distribution of immunostaining in activated macrophages compared with macrophages of WKY lungs. Overall, AIF1 immunostaining demonstrated reproducible macrophage staining across multiple species and tissue types. Given the increasing breadth of model species used to study human disease, the use of cross-species markers and techniques can reduce some of the inherent variability within translational research.
同种异体移植炎症因子1(AIF1)是人类和一些动物模型大脑中常用的小胶质细胞标志物,但在其他地方的应用有限。我们试图确定AIF1是否可以作为常见实验动物物种和组织中的巨噬细胞标志物。我们通过使用先前在人体组织中验证过的AIF1免疫染色技术,研究了具有明确巨噬细胞群体的组织(即脾脏、肝脏和肺)。组织取自各种小鼠品系(n = 20)、大鼠品系(n = 15)、猪(n = 4)、雪貂(n = 4)和人类(n = 4,仅肺组织)。所有肝脏样本在间质细胞中都有散在的免疫染色,与驻留组织巨噬细胞(库普弗细胞)一致。脾脏样本在红髓和白髓区室中都有巨噬细胞的细胞免疫染色,但红髓中有更多免疫染色的细胞聚集物,并且在某些物种中,与白髓相比免疫染色强度增加。在肺中,肺泡巨噬细胞染色较弱至中等,而间质和血管周围巨噬细胞染色中等至强烈。在一些切片中检测到偶然的病变和组织变化,包括肿瘤、诱导性支气管相关淋巴组织以及显示巨噬细胞AIF1免疫染色的炎症病变。最后,我们比较了高血压大鼠模型(SHR品系)和正常血压模型(WKY品系)之间肺泡巨噬细胞的AIF1免疫染色。与WKY肺的巨噬细胞相比,SHR肺中活化巨噬细胞的免疫染色强度和分布发生了改变。总体而言,AIF1免疫染色在多个物种和组织类型中显示出可重复的巨噬细胞染色。鉴于用于研究人类疾病的模型物种范围不断扩大,使用跨物种标志物和技术可以减少转化研究中一些固有的变异性。