Bauer Susanne, Abdgawad Mohamed, Gunnarsson Lena, Segelmark Mårten, Tapper Hans, Hellmark Thomas
Department of Clinical Sciences, Clinical Sciences in Lund, Lund University, 221 84 Lund, Sweden.
J Leukoc Biol. 2007 Feb;81(2):458-64. doi: 10.1189/jlb.0806514. Epub 2006 Oct 31.
Proteinase 3 (PR3) is found in granules of all neutrophils but also on the plasma membrane of a subset of neutrophils (mPR3). CD177, another neutrophil protein, also displays a bimodal surface expression. In this study, we have investigated the coexpression of these two molecules, as well as the effect of cell activation on their surface expression. We can show that CD177 is expressed on the same subset of neutrophils as mPR3. Experiments show that the expression of mPR3 and CD177 on the plasma membrane is increased or decreased in parallel during cell stimulation or spontaneous apoptosis. Furthermore, we observed a rapid internalization and recirculation of mPR3 and plasma membrane CD177, where all mPR3 is replaced within 30 min. Our findings suggest that the PR3 found on the plasma membrane has its origin in the same intracellular storage as CD177, i.e., secondary granules and secretory vesicles and not primary granules. PR3- and CD177-expressing neutrophils constitute a subpopulation of neutrophils with an unknown role in the innate immune system, which may play an important role in diseases such as Wegener's granulomatosis and polycythemia vera.
蛋白酶3（PR3）存在于所有中性粒细胞的颗粒中，但也存在于一部分中性粒细胞的质膜上（mPR3）。另一种中性粒细胞蛋白CD177也呈现双峰表面表达。在本研究中，我们研究了这两种分子的共表达情况，以及细胞活化对其表面表达的影响。我们发现CD177与mPR3在相同的中性粒细胞亚群上表达。实验表明，在细胞刺激或自发凋亡过程中，质膜上mPR3和CD177的表达会同时升高或降低。此外，我们观察到mPR3和质膜CD177会迅速内化和再循环，其中所有mPR3在30分钟内被替换。我们的研究结果表明，质膜上发现的PR3与CD177起源于相同的细胞内储存部位，即次级颗粒和分泌小泡，而非初级颗粒。表达PR3和CD177的中性粒细胞构成了中性粒细胞的一个亚群，在先天免疫系统中的作用尚不清楚，可能在韦格纳肉芽肿和真性红细胞增多症等疾病中起重要作用。
