Association between macrophage activation and function of micro-encapsulated rat islets
Association between macrophage activation and function of micro-encapsulated rat islets
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DOI：
10.1007/s00125-003-1087-7
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发表时间：
2003-05-01
期刊：
影响因子：
8.2
通讯作者：
de Haan, BJ
中科院分区：
文献类型：
--
作者：
de Vos, P;Smedema, I;de Haan, BJ
目的/假设。微囊化胰岛移植物的存活是有限的，即使当针对囊的炎症反应被限制在小于10%的一小部分时。本研究调查了在体内大鼠受体和体外细胞过度生长是否对这少数胶囊有助于限制90%的包囊胰岛的功能存活，其保持无任何细胞过度生长。在同种异体微囊化胰岛移植物的成功大鼠接受者中，我们发现囊内过度生长的绝大多数细胞是活化的艾德-1和艾德-2阳性巨噬细胞，其数量约为1500个/囊。每个胶囊含1500（nr 8383）个大鼠巨噬细胞的包囊化胰岛的共培养表明，巨噬细胞的活化是由胰岛源性生物活性因子引起的，因为巨噬细胞分泌TNF-α和IL-1 β是由含胰岛的胶囊而不是空胶囊诱导的。巨噬细胞的这种激活与封装的胰岛的功能的减少有关，如在静态孵育中定量减少（35%）的胰岛素响应和在灌注中较慢的响应所证明的。目前的研究旨在设计暂时抑制巨噬细胞活化的策略，因为巨噬细胞主要存在于植入后的前两个月。这些策略将为微囊化胰岛的临床应用提供相关依据。
Aims/hypothesis. Survival of microencapsulated islet grafts is limited, even when inflammatory reactions against the capsules are restricted to a small portion of less than 10%.Methods. This study investigates both in vivo in rat recipients and in vitro whether cellular overgrowth on this minority of the capsules contributes to limitations in the functional survival of the 90% of the encapsulated islets which remain free of any cellular overgrowth.Results. In successful rat recipients of an allogenic microencapsulated islet graft we found that the vast majority of cells in the capsular overgrowth were activated ED-1 and ED-2 positive macrophages which were found in numbers of approximately 1500 per capsule. Co-culture of encapsulated islets with 1500 (nr8383) rat-macrophages per capsule showed that the activation of macrophages was caused by islet-derived bioactive factors since TNF-alpha and IL-1beta secretion by macrophages was induced by islet-containing capsules and not by empty capsules. This activation of macrophages was associated with a decrease in function of the encapsulated islets as evidenced by a quantitatively reduced (35%) insulin response in static incubation and a slower response in perifusion.Conclusion/interpretation. Present research aims to design strategies for the temporary inhibition of macrophage activation since macrophages are predominantly present in the first two months after implantation. These strategies will serve as a pertinent basis for future clinical application of microencapsulated islets.