Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands.
Cell Microbiol. 2013 Oct;15(10):1753-65. doi: 10.1111/cmi.12147. Epub 2013 May 3.
Neutrophil recruitment is essential in clearing pneumococcal infections. The first step in neutrophil extravasation involves the interaction between P-selectin on activated endothelium and P-Selectin Glycoprotein 1 (PSGL-1) on neutrophils. Here, we identify pneumococcal Zinc metalloproteinase C as a potent inhibitor of PSGL-1. ZmpC degrades the N-terminal domain of PSGL-1, thereby disrupting the initial rolling of neutrophils on activated human umbilical vein endothelial cells. Furthermore, mice infected with wild-type strain in the model of pneumococcal pneumonia showed lower lungs neutrophil infiltration compare to animals infected with ZmpC mutant. In addition, we confirmed the association of zmpC with serotype 8 and 11A and found it to be associated with serotype 33F as well. In conclusion, wereport PSGL-1 as a novel target for ZmpC and show that ZmpC inhibits neutrophil extravasation during pneumococcal pneumonia.
中性粒细胞募集对于清除肺炎链球菌感染至关重要。中性粒细胞外渗的第一步涉及激活的内皮细胞上的 P 选择素与中性粒细胞上的 P-选择素糖蛋白 1（PSGL-1）之间的相互作用。在这里，我们确定肺炎链球菌锌金属蛋白酶 C 是 PSGL-1 的有效抑制剂。ZmpC 降解 PSGL-1 的 N 端结构域，从而破坏中性粒细胞在激活的人脐静脉内皮细胞上的初始滚动。此外，与感染 ZmpC 突变株的动物相比，在肺炎链球菌肺炎模型中感染野生型菌株的小鼠肺部中性粒细胞浸润减少。此外，我们证实了 zmpC 与 8 型和 11A 型的关联，并发现它也与 33F 型相关。总之，我们报道 PSGL-1 是 ZmpC 的一个新靶标，并表明 ZmpC 在肺炎链球菌性肺炎期间抑制中性粒细胞外渗。
