Inhibition of gelatinase B (matrix metalloprotease-9) activity reduces cellular inflammation and restores function of transplanted pancreatic islets.
Inhibition of gelatinase B (matrix metalloprotease-9) activity reduces cellular inflammation and restores function of transplanted pancreatic islets.
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作者：
Lingwal N;Padmasekar M;Samikannu B;Bretzel RG;Preissner KT;Linn T
胰岛移植为1型糖尿病患者提供了一种补偿胰岛素生成细胞损失的方法。然而，门静脉内移植途径与移植物的即时炎症反应和随后的胰岛破坏有关。虽然基质金属蛋白酶(MMP)-2和-9参与细胞外基质的重塑和白细胞迁移，但它们对胰岛移植结果的影响尚未明确。我们在对照组和移植组小鼠中观察到相似的MMP-2 mRNA表达，而胰岛移植后MMP-9 mRNA和蛋白表达水平升高。对表达CD11b （Mac-1）的白细胞（巨噬细胞、中性粒细胞）和Ly6G（中性粒细胞）的免疫染色显示，在MMP-9敲除受体中，炎症细胞向胰岛移植肝脏的迁移显著减少。此外，与对照组相比，明胶酶抑制导致移植胰岛胰岛素含量显著增加，巨噬细胞和中性粒细胞内流减少。这些结果表明，胰岛移植后MMP-9表达和活性的增加与白细胞迁移的增强直接相关，抑制MMP-9（明胶酶B）活性可改善胰岛移植早期存活。
Islet transplantation provides an approach to compensate for loss of insulin-producing cells in patients with type 1 diabetes. However, the intraportal route of transplantation is associated with instant inflammatory reactions to the graft and subsequent islet destruction as well. Although matrix metalloprotease (MMP)-2 and -9 are involved in both remodeling of extracellular matrix and leukocyte migration, their influence on the outcome of islet transplantation has not been characterized. We observed comparable MMP-2 mRNA expressions in control and transplanted groups of mice, whereas MMP-9 mRNA and protein expression levels increased after islet transplantation. Immunostaining for CD11b (Mac-1)-expressing leukocytes (macrophage, neutrophils) and Ly6G (neutrophils) revealed substantially reduced inflammatory cell migration into islet-transplanted liver in MMP-9 knockout recipients. Moreover, gelatinase inhibition resulted in a significant increase in the insulin content of transplanted pancreatic islets and reduced macrophage and neutrophil influx compared with the control group. These results indicate that the increase of MMP-9 expression and activity after islet transplantation is directly related to enhanced leukocyte migration and that early islet graft survival can be improved by inhibiting MMP-9 (gelatinase B) activity.
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影响因子：
6.2
作者：
Lutz, J;Yao, YS;Heemann, U
通讯作者：
Heemann, U
DOI：
10.1152/ajpheart.00447.2006
发表时间：
2007-06-01
影响因子：
4.8
作者：
Brower, Gregory L.;Levick, Scott P.;Janicki, Joseph S.
通讯作者：
Janicki, Joseph S.
人类嗜中性粒细胞衍生的组织蛋白酶G和Azurocidin/cap37鉴定为单核细胞和中性粒细胞的趋化剂。
DOI：
10.1084/jem.186.5.739
发表时间：
1997-08-29
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Chertov O;Ueda H;Xu LL;Tani K;Murphy WJ;Wang JM;Howard OM;Sayers TJ;Oppenheim JJ
通讯作者：
Oppenheim JJ
影响因子：
15.9
作者：
Dubois, B;Masure, S;Arnold, B
通讯作者：
Arnold, B
影响因子：
4.4
作者：
Bennouna, S;Bliss, SK;Denkers, EY
通讯作者：
Denkers, EY