Hughes Stephen J, Clark Anne, McShane Philip, Contractor Harold H, Gray Derek W R, Johnson Paul R V
Islet Transplant Research Group, Nuffield Department of Surgery, University of Oxford, Oxford, United Kingdom.
Transplantation. 2006 Feb 15;81(3):423-6. doi: 10.1097/01.tp.0000197482.91227.df.
To optimize the methods used for human islet isolation for transplantation, it is important to improve our understanding of the structure of the islet-exocrine interface. In this study, the composition of collagen subtypes in the interface have been characterized and quantified in human pancreas.
Human adult pancreases were retrieved from older (mean age 55.7+/-3.0 yrs) and young donors (mean age 21.8+/-3.2 yrs). Tissue from the body of each pancreas was examined by quantitative immunohistochemistry. Collagen within the islet-exocrine interface was identified by immunolabeling for collagen I, IV, V or VI and islets identified either morphologically or by immunolabeling for insulin. Collagen subtypes were quantified and data expressed as collagen area at the interface relative to the islet area. Statistical analysis was by ANOVA or Mann Whitney U test.
In older pancreases, collagen IV, V and VI were present throughout the islet-exocrine interface, whereas collagen I was more variable. The mean peri-islet collagen VI proportion was significantly greater than that of collagen I or IV. Mean islet area and the proportional collagen VI content in specimens from younger subjects were not significantly different to those in older subjects.
Collagen VI is a major component of the islet-exocrine interface of the adult pancreas, the content being more than double that of collagen I or IV. However, the proportional collagen VI content was not dependent on the age of the donor. These data may facilitate the design of new collagenases, targeting major substrates such as collagen VI in order to improve clinical islet isolation.
为优化用于移植的人胰岛分离方法,加深对胰岛 - 外分泌腺界面结构的理解很重要。在本研究中,已对人胰腺中该界面的胶原亚型组成进行了表征和定量分析。
从老年(平均年龄55.7±3.0岁)和年轻供体(平均年龄21.8±3.2岁)获取成人胰腺。通过定量免疫组织化学检查每个胰腺体部的组织。通过对I、IV、V或VI型胶原进行免疫标记来鉴定胰岛 - 外分泌腺界面内的胶原,通过形态学或胰岛素免疫标记来鉴定胰岛。对胶原亚型进行定量分析,数据表示为界面处胶原面积相对于胰岛面积的比例。采用方差分析或曼 - 惠特尼U检验进行统计分析。
在老年胰腺中,IV、V和VI型胶原存在于整个胰岛 - 外分泌腺界面,而I型胶原的分布更具变异性。胰岛周围VI型胶原的平均比例显著高于I型或IV型胶原。年轻受试者标本中的平均胰岛面积和VI型胶原的比例含量与老年受试者相比无显著差异。
VI型胶原是成人胰腺胰岛 - 外分泌腺界面的主要成分,其含量是I型或IV型胶原的两倍多。然而,VI型胶原的比例含量并不依赖于供体年龄。这些数据可能有助于设计新的胶原酶,以主要底物如VI型胶原为靶点,从而改善临床胰岛分离。