Hom J T, Estridge T, Pechous P, Hyslop P A
Cardiovascular Research, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46285, USA.
J Leukoc Biol. 1995 Nov;58(5):526-32. doi: 10.1002/jlb.58.5.526.
The amyloidogenic peptides, amyloid-beta (A beta) and human amylin, are the major constituents of amyloid deposits found in patients with the chronic degenerative disorders Alzheimer's disease (AD) and type 2 diabetes, respectively. Recent studies have shown that a variety of inflammatory proteins such as cytokines are associated with the amyloid deposits of AD brain tissues. Therefore, in the present study, we sought to determine whether A beta and/or human amylin could modulate the various inflammatory activities of eosinophils. We observed that human amylin but not A beta peptides inhibited the in vitro interleukin-5 (IL-5)-mediated survival of cord blood-derived eosinophils (CBEs) in a concentration-dependent manner. By contrast, rat amylin, a nonamyloidogenic peptide that is highly homologous to human amylin, failed to affect the IL-5-mediated survival of CBEs. Similar inhibitory effects of human amylin were observed for peripheral blood eosinophils. Human amylin also enhanced the release of the cytokine granulocyte-macrophage colony-stimulating factor by CBEs that were stimulated with the calcium ionophore A23187 but was incapable of directly stimulating CBEs to release cytokines. In addition, the A23187-induced release of the inflammatory lipid mediator leukotriene C4 by CBEs was augmented by human amylin. These results suggest that the amyloidogenic peptide human amylin is capable of amplifying the various inflammatory activities of eosinophils.
淀粉样蛋白生成肽，β-淀粉样蛋白（Aβ）和人胰岛淀粉样多肽，分别是慢性退行性疾病阿尔茨海默病（AD）和2型糖尿病患者淀粉样沉积物的主要成分。最近的研究表明，多种炎症蛋白如细胞因子与AD脑组织的淀粉样沉积物有关。因此，在本研究中，我们试图确定Aβ和/或人胰岛淀粉样多肽是否能调节嗜酸性粒细胞的各种炎症活性。我们观察到，人胰岛淀粉样多肽而非Aβ肽以浓度依赖的方式抑制体外白细胞介素-5（IL-5）介导的脐血来源嗜酸性粒细胞（CBE）的存活。相比之下，与人类胰岛淀粉样多肽高度同源的非淀粉样蛋白生成肽大鼠胰岛淀粉样多肽未能影响IL-5介导的CBE存活。人胰岛淀粉样多肽对外周血嗜酸性粒细胞也有类似的抑制作用。人胰岛淀粉样多肽还增强了用钙离子载体A23187刺激的CBE释放细胞因子粒细胞-巨噬细胞集落刺激因子的能力，但不能直接刺激CBE释放细胞因子。此外，人胰岛淀粉样多肽增强了A23187诱导的CBE释放炎症脂质介质白三烯C4的能力。这些结果表明，淀粉样蛋白生成肽人胰岛淀粉样多肽能够增强嗜酸性粒细胞的各种炎症活性。
