Josefsen K, Nielsen H, Hansen W A, Kristensen J K, Bilde T, Bendtzen K, Buschard K
Bartholin Institute, Kommunehospitalet, Copenhagen, Denmark.
Life Sci. 1995 Mar 10;56(16):1333-42. doi: 10.1016/0024-3205(95)00085-2.
Macrophages play a major role in the pathogenesis of insulin-dependent diabetes mellitus in animals. These cells are the first to invade the pancreas and macrophage-eradicating treatments reduce the incidence of the disease. In humans, however, their role is less clear. In this study we investigated the hypothesis that the pancreatic environment per se could activate macrophages. Tissue culture supernatants from human islets of Langerhans were tested for chemotactic activity and oxidative burst response in monocytes isolated from healthy adults. Preincubation with the supernatants enhanced the oxidative burst response evoked by fMLP (up to 379%) and opsonized zymosan (up to 173%). The activity decreased by dilution and was no longer detectable at 1:16. No increased activity was seen in supernatants from a number of other human endocrine and non-endocrine primary cells, suggesting a factor specific for islet tissue. The increased oxidative burst response could partially be eliminated by heat- and proteinase K treatment, suggesting that the activity could be of polypeptide nature. The factor could not be absorbed by polyvalent rabbit antibodies directed towards a variety of cytokines not by a mixture of high-titer anti-cytokine antibodies. It is possible that islet factors could also promote such monocyte activation in vivo in monocytes attracted to the islets of Langerhans by other means. This could contribute to the development of insulin-dependent diabetes in humans.
巨噬细胞在动物胰岛素依赖型糖尿病的发病机制中起主要作用。这些细胞是最先侵入胰腺的，而清除巨噬细胞的治疗可降低该病的发病率。然而，在人类中，它们的作用尚不清楚。在本研究中，我们调查了胰腺环境本身可激活巨噬细胞这一假说。检测了来自人胰岛的组织培养上清液对从健康成年人分离的单核细胞的趋化活性和氧化爆发反应。用上清液预孵育增强了由fMLP（高达379%）和调理酵母聚糖（高达173%）诱发的氧化爆发反应。该活性随稀释而降低，在1:16时不再可检测到。在许多其他人类内分泌和非内分泌原代细胞的上清液中未观察到活性增加，提示存在一种胰岛组织特异性因子。热和蛋白酶K处理可部分消除氧化爆发反应的增加，提示该活性可能具有多肽性质。该因子不能被针对多种细胞因子的多价兔抗体吸收，也不能被高滴度抗细胞因子抗体混合物吸收。胰岛因子也有可能在体内促进被其他方式吸引到胰岛的单核细胞的这种激活。这可能有助于人类胰岛素依赖型糖尿病的发展。
