Intracellular and Cell Surface Localization of a Complex between αMβ2 Integrin and Promatrix Metalloproteinase-9 Progelatinase in Neutrophils1
Intracellular and Cell Surface Localization of a Complex between αMβ2 Integrin and Promatrix Metalloproteinase-9 Progelatinase in Neutrophils1
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中性粒细胞中 αMβ2 整合素和 Promatrix Metallo Proteinase-9 Progelatinase 复合物的细胞内和细胞表面定位1
DOI：
10.4049/jimmunol.172.11.7060
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发表时间：
2004
期刊：
影响因子：
--
通讯作者：
E. Koivunen
中科院分区：
文献类型：
--
作者：
Michael Stefanidakis;T. Ruohtula;N. Borregaard;C. Gahmberg;E. Koivunen
我们最近发现前基质金属蛋白酶（promatrix metalloproteinases，proMMPs），特别是proMMP-9，是白细胞β2整合素的有效配体。我们在此研究了proMMP-9和αMβ2之间的复合物形成，α Mβ2是中性粒细胞的主要MMP和整合素。在静息中性粒细胞上，proMMP-9/αMβ2复合物主要在细胞内颗粒中检测到，但在细胞活化后，其定位于细胞表面，如免疫沉淀和双重免疫荧光所示。复合物形成的进一步迹象是中性粒细胞和αMβ2转染的L细胞，而不是野生型L细胞或白细胞粘附缺陷细胞，以β2整合素依赖性方式结合固定化proMMP-9或其重组催化结构域。结合αM整合素-I结构域并抑制其与proMMP-9形成复合物的肽在体外跨内皮测定和体内巯基乙酸盐诱导的腹膜炎中阻止中性粒细胞迁移。这些结果表明，易位proMMP-9/αMβ2复合物可能是引导中性粒细胞迁移的细胞表面机制的一部分。
We have recently demonstrated that promatrix metalloproteinases (proMMPs), particularly proMMP-9, are potent ligands of the leukocyte β2 integrins. We studied here the complex formation between proMMP-9 and αMβ2, the major MMP and integrin of neutrophils. On resting neutrophils, the proMMP-9/αMβ2 complex was primarily detected in intracellular granules, but after cellular activation it became localized to the cell surface, as demonstrated by immunoprecipitation and double immunofluorescence. Further indication of the complex formation was that neutrophils and αMβ2-transfected L cells, but not the wild-type L cells or leukocyte adhesion deficiency cells, bound to immobilized proMMP-9 or its recombinant catalytic domain in a β2 integrin-dependent manner. Peptides that bound to the αM integrin-I domain and inhibited its complex formation with proMMP-9 prevented neutrophil migration in a transendothelial assay in vitro and in a thioglycolate-elicited peritonitis in vivo. These results suggest that the translocating proMMP-9/αMβ2 complex may be part of the cell surface machinery guiding neutrophil migration.
影响因子：
20.3
作者：
Pluskota, E;Soloviev, DA;Plow, EF
通讯作者：
Plow, EF
人中性粒细胞在趋化迁移过程中不会降解主要的基底膜成分。
DOI：
10.1016/s1357-2725(97)00038-1
发表时间：
1997
期刊：
The international journal of biochemistry & cell biology
影响因子：
--
作者：
Steadman,R;StJohn,PL;Evans,RA;Thomas,GJ;Davies,M;Heck,LW;Abrahamson,DR
通讯作者：
Abrahamson,DR
影响因子：
10.5
作者：
Yu, Q;Stamenkovic, I
通讯作者：
Stamenkovic, I