Research Group Neuro-endocrine-immune Interactions, Institute of Anatomy, University of Zürich, Zürich, Switzerland.
Immunology. 2009 Nov;128(3):342-50. doi: 10.1111/j.1365-2567.2009.03136.x.
Insulin-like growth factor I (IGF-I) is a potent hormone that stimulates growth and differentiation and inhibits apoptosis in numerous tissues. Preliminary evidence suggests that IGF-I exerts differentiating, mitogenic and restoring activities in the immune system but the sites of synthesis of local IGF-I are unknown. Identification of these sites would allow the functional role of local IGF-I to be clarified. The presence of IGF-I in non-immune cells suggests that it acts as a trophic factor, while its occurrence in subtypes of lymphocytes or antigen-presenting cells indicates paracrine/autocrine direct regulatory involvement of IGF-I in the human immune response. The present study investigated the location of IGF-I messenger RNA and protein on archival human lymph node samples by in situ hybridization, immunohistochemistry and double immunofluorescence staining using an IGF-I probe and antisera specific for human IGF-I and CD3 (T lymphocytes), CD20 (B lymphocytes), CD68 (macrophages), CD21 (follicular dendritic cells), S100 (interdigitating dendritic cells) and podoplanin (fibroblastic reticular cells). Numerous cells within the B- and T-cell compartments expressed the IGF-I gene, and the majority of these cells were identified as macrophages. Solitary follicular dendritic cells exhibited IGF-I. A few T lymphocytes, and no B lymphocytes, contained IGF-I immunoreactive material. Furthermore, IGF-I immunoreactive cells outside the follicles that did not react with CD3, CD20, S100 or podoplanin markers were identified as high-endothelial venule (HEV) cells. From this we conclude that the main task of IGF-I in human non-tumoral lymph node may be autocrine and paracrine regulation of the differentiation, stimulation and survival of lymphocytes, antigen-presenting cells and macrophages and the differentiation and maintenance of HEV cells.
胰岛素样生长因子 I（IGF-I）是一种有效的激素，可刺激多种组织的生长和分化并抑制细胞凋亡。初步证据表明，IGF-I 在免疫系统中发挥分化、有丝分裂和恢复作用，但局部 IGF-I 的合成部位尚不清楚。确定这些部位将有助于阐明局部 IGF-I 的功能作用。非免疫细胞中存在 IGF-I 表明它作为营养因子发挥作用，而其在淋巴细胞或抗原呈递细胞的亚型中出现表明 IGF-I 以旁分泌/自分泌的方式直接参与人类免疫反应的调节。本研究通过原位杂交、免疫组织化学和双重免疫荧光染色，使用 IGF-I 探针和针对人 IGF-I 和 CD3（T 淋巴细胞）、CD20（B 淋巴细胞）、CD68（巨噬细胞）、CD21（滤泡树突状细胞）、S100（交错树突状细胞）和 podoplanin（成纤维细胞网状细胞）的抗血清，研究了 IGF-I 信使 RNA 和蛋白质在存档的人淋巴结样本中的位置。B 和 T 细胞区室中的许多细胞表达 IGF-I 基因，其中大多数细胞被鉴定为巨噬细胞。孤立的滤泡树突状细胞表现出 IGF-I。少数 T 淋巴细胞，没有 B 淋巴细胞，含有 IGF-I 免疫反应性物质。此外，在不与 CD3、CD20、S100 或 podoplanin 标志物反应的滤泡外发现的 IGF-I 免疫反应性细胞被鉴定为高内皮小静脉（HEV）细胞。由此我们得出结论，IGF-I 在人类非肿瘤性淋巴结中的主要任务可能是对淋巴细胞、抗原呈递细胞和巨噬细胞的分化、刺激和存活以及 HEV 细胞的分化和维持进行自分泌和旁分泌调节。
