Kolaczkowska Elzbieta, Lelito Monika, Kozakiewicz Elzbieta, van Rooijen Nico, Plytycz Barbara, Arnold Bernd
Department of Evolutionary Immunobiology, Institute of Zoology, Jagiellonian University, ul. Ingardena 6, PL-30-060 Krakow, Poland.
Immunol Lett. 2007 Nov 15;113(2):99-106. doi: 10.1016/j.imlet.2007.07.017. Epub 2007 Aug 24.
Metalloproteinase 9 (MMP-9) is crucial for normal neutrophil infiltration into zymosan-inflamed peritoneum. During the course of zymosan peritonitis MMP-9 is produced in a biphasic-manner as its presence is detectable as early as 30 min post zymosan and then between 2 and 8 h of inflammation. As inflammatory leukocytes were shown to produce MMP-9 we asked if also resident leukocytes, mast cells and macrophages, contribute to its production. And furthermore, if their contribution is limited only to the early phase of inflammation or extends to the later stages. For this purpose some mice were depleted of either resident macrophages or functional mast cells and expression of MMP-9 in peritoneal leukocytes and its release to the exudate were monitored. It turned out that depletion of peritoneal macrophages decreased both MMP-9 content in the leukocytes and its release to the inflammatory exudate at 30 min and 6h of peritonitis. The functional depletion of mast cells also caused a significant decrease in the production/release of MMP-9 that was especially apparent at the early time point (30 min). Moreover, the study shows concomitant kinetics of MMP-9 expression in leukocytes and its release to the exudatory fluid. The findings indicate that resident tissue leukocytes, and among them especially macrophages, constitute an important source of MMP-9 during acute peritoneal inflammation. Overall, the study shows that resident tissue leukocytes, mostly macrophages, constitute an important cellular source(s) of inflammation-related factors and should be regarded as possible targets of anti-inflammatory treatment.
金属蛋白酶9（MMP - 9）对于中性粒细胞正常浸润至酵母聚糖诱发炎症的腹膜至关重要。在酵母聚糖诱发腹膜炎的过程中，MMP - 9以双相方式产生，因为早在酵母聚糖注射后30分钟就能检测到其存在，然后在炎症发生的2至8小时之间也能检测到。由于炎症白细胞已被证明可产生MMP - 9，我们不禁要问，常驻白细胞、肥大细胞和巨噬细胞是否也对其产生有贡献。此外，它们的贡献是否仅局限于炎症的早期阶段，还是会延伸至后期阶段。为此，一些小鼠被清除了常驻巨噬细胞或功能性肥大细胞，并监测了腹膜白细胞中MMP - 9的表达及其向渗出液中的释放情况。结果发现，在腹膜炎30分钟和6小时时，腹膜巨噬细胞的清除降低了白细胞中MMP - 9的含量及其向炎性渗出液中的释放。肥大细胞的功能缺失也导致MMP - 9的产生/释放显著减少，这在早期时间点（30分钟）尤为明显。此外，该研究显示了白细胞中MMP - 9表达及其向渗出液中释放的伴随动力学。这些发现表明，常驻组织白细胞，尤其是其中的巨噬细胞，在急性腹膜炎症期间构成了MMP - 9的重要来源。总体而言，该研究表明常驻组织白细胞，主要是巨噬细胞，构成了炎症相关因子的重要细胞来源，应被视为抗炎治疗的可能靶点。
