de Groot Martijn, Schuurs Theo A, Leuvenink Henri G D, van Schilfgaarde Reinout
Surgical Research Laboratory, Department of Surgery, Groningen University Hospital, Groningen, The Netherlands.
J Surg Res. 2003 Dec;115(2):235-41. doi: 10.1016/j.jss.2003.07.008.
Encapsulation significantly prolongs islet graft survival in the absence of immunosuppression. However, encapsulated islet graft survival is limited to periods of several months. Part of the encapsulated islet graft is affected by a nonprogressive pericapsular overgrowth. To investigate whether macrophages on overgrown capsules affect neighboring nonovergrown encapsulated islets, encapsulated islets were studied during coculture.
Encapsulated islet function, islet vitality, and islet cell replication were assessed, as well as the mRNA expression of Bcl-2, Bax, inducible nitric oxide synthase, and monocyte chemoattractant protein-1 in encapsulated islets after 48 h of culture together with microcapsules with macrophage overgrowth. Overgrown capsules were retrieved from the rat peritoneum, three weeks after implantation of an encapsulated islet graft.
Coculture was associated with inhibition of the stimulated insulin secretion, with decreased cell replication, and with increased cell necrosis, but not with apoptosis of encapsulated islet cells. mRNA expression levels in encapsulated islets after coculture were not different from controls, except for a decrease in Bax mRNA. We found a high level of nitrite, as an indicator of nitric oxide production, but not an increase in inducible nitric oxide synthase mRNA in islets. This, in combination with the absence of increase in monocyte chemoattractant protein-1 mRNA and the lack of apoptosis, indicates that neither interleukin-1beta nor tumor necrosis factor-alpha was responsible for the deleterious effects of coculture on encapsulated islets.
Nonovergrown encapsulated islets are affected by the overgrowth on encapsulated islets in their close proximity. This overgrowth contains macrophages that produce nitric oxide which, rather than cytokines, may be held responsible for the deleterious effect on the neighboring encapsulated islets.
在无免疫抑制的情况下，胰岛包封可显著延长胰岛移植的存活时间。然而，包封胰岛移植的存活时间仅限于几个月。部分包封胰岛移植受到非进行性的囊周过度生长的影响。为了研究过度生长的包囊上的巨噬细胞是否会影响相邻未过度生长的包封胰岛，在共培养过程中对包封胰岛进行了研究。
评估包封胰岛的功能、活力和胰岛细胞复制情况，以及在与有巨噬细胞过度生长的微胶囊共培养48小时后，包封胰岛中Bcl-2、Bax、诱导型一氧化氮合酶和单核细胞趋化蛋白-1的mRNA表达。在植入包封胰岛移植三周后，从大鼠腹膜中取出过度生长的包囊。
共培养与刺激胰岛素分泌的抑制、细胞复制减少和细胞坏死增加有关，但与包封胰岛细胞的凋亡无关。共培养后包封胰岛中的mRNA表达水平与对照组无差异，除了Bax mRNA有所下降。我们发现亚硝酸盐水平较高，作为一氧化氮产生的指标，但胰岛中诱导型一氧化氮合酶mRNA没有增加。这与单核细胞趋化蛋白-1 mRNA没有增加以及缺乏凋亡相结合，表明白细胞介素-1β和肿瘤坏死因子-α均不是共培养对包封胰岛产生有害影响的原因。
未过度生长的包封胰岛会受到其附近包封胰岛过度生长的影响。这种过度生长含有产生一氧化氮的巨噬细胞，可能是一氧化氮而非细胞因子对相邻包封胰岛产生了有害影响。
