Resistin and resistin-like molecules are pleiotropic cytokines that are involved in inflammatory diseases. Our previous work suggested that resistin has the potential to be used as a biomarker and therapeutic target for human pulmonary arterial hypertension. However, data are limited on the distribution of resistin in healthy human organs. In this study, we used our newly developed anti-human resistin (hResistin) antibody to immunohistochemically detect the expression, localization, and intracellular/extracellular compartmentalization of hResistin in a full human tissue panel from healthy individuals. The potential cross reactivity of this monoclonal anti-hResistin IgG1 with normal human tissues also was verified. Results showed that hResistin is broadly distributed and principally localized in the cytoplasmic granules of macrophages scattered in the interstitium of most human tissues. Bone marrow hematopoietic precursor cells also exhibited hResistin signals in their cytoplasmic granules. Additionally, hResistin labeling was observed in the cytoplasm of nervous system cells. Notably, the cytokine activity of hResistin was illustrated by positively stained extracellular material in most human tissues. These data indicate that our generated antibody binds to the secreted hResistin and support its potential use for immunotherapy to reduce circulating hResistin levels in human disease. Our findings comprehensively document the basal expression patterns of hResistin protein in normal human tissues, suggest a critical role of this cytokine in normal and pathophysiologic inflammatory processes, and offer key insights for using our antibody in future pharmacokinetic studies and immunotherapeutic strategies.

抵抗素和类似抵抗素的分子是参与炎症性疾病的多效性细胞因子。我们以前的工作表明抵抗素有潜力用作人类肺动脉高压的生物标志物和治疗靶标。但是，关于抵抗素在健康人体器官中的分布的数据有限。在这项研究中，我们使用了我们新开发的抗人抵抗素（hResistin）抗体，通过免疫组化从健康个体中检测了hResistin在整个人体组织中的表达，定位以及细胞内/细胞外区室化。还验证了这种单克隆抗hResistin IgG1与正常人组织的潜在交叉反应性。结果表明，hResistin广泛分布并主要分布在散布在大多数人组织间质中的巨噬细胞的胞质颗粒中。骨髓造血前体细胞在其细胞质颗粒中也表现出hResistin信号。此外，在神经系统细胞的细胞质中观察到了hResistin标记。值得注意的是，hResistin的细胞因子活性可以通过大多数人组织中阳性染色的细胞外物质来说明。这些数据表明我们产生的抗体与分泌的hResistin结合，并支持其在免疫治疗中降低人类疾病中循环hResistin水平的潜在用途。我们的发现全面记录了hResistin蛋白在正常人体组织中的基础表达模式，