Basophils preferentially express mouse mast cell protease 11 among the mast cell tryptase family in contrast to mast cells

Basophils preferentially express mouse mast cell protease 11 among the mast cell tryptase family in contrast to mast cells
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DOI:
10.1189/jlb.0609400
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发表时间:
2009-12-01
影响因子:
5.5
通讯作者:
Karasuyama, Hajime
Karasuyama, Hajime
中科院分区:
医学3区
文献类型:
--
作者:
Ugajin, Tsukasa;Kojima, Toshiyuki;Karasuyama, Hajime

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类胰蛋白酶和糜酶是肥大细胞储存和分泌的主要蛋白质,具有多种生物学功能。然而,嗜碱性粒细胞产生的蛋白酶的性质一直没有得到很好的表征,特别是在小鼠身上。MMCP-11是最近在小鼠体内发现的肥大细胞类胰蛋白酶,最初被鉴定为Prss 34,在一些肥大细胞样细胞系中转录,并在BMMC与IL-3共同培养的早期阶段转录。奇怪的是,与其他肥大细胞类胰蛋白酶相比,Prss 34在正常组织中优先在骨髓和脾组织中表达。因此,在体内表达mMCP-11的细胞类型仍然难以捉摸。在这里,我们发现mMCP-11在原代嗜碱性粒细胞中高表达,在一些肥大细胞中低表达。Prs34转录本在原代和培养的嗜碱性粒细胞中大量表达,在腹膜肥大细胞或培养的BMMC中表达很弱。相反,mMCP-6和mMCP-7类胰蛋白酶的转录本在培养的和腹膜肥大细胞中优先表达,而不是嗜碱性粒细胞。我们建立了mMCP-11的特异性mAb,结果表明mMCP-11蛋白确实由初级嗜碱性粒细胞和那些在变态反应性炎症和寄生虫感染过程中渗入受影响组织的嗜碱性粒细胞表达。一些原代肥大细胞也表达mMCP-11蛋白,尽管表达水平要低得多。因此,嗜碱性粒细胞而不是肥大细胞是mMCP-11的主要来源。这是第一个证明小鼠嗜碱性粒细胞产生类胰蛋白酶的研究。J.Leukoc。比奥尔。86:1417-1425;2009。
Tryptases and chymases are the major proteins stored and secreted by mast cells, and they have various biological functions. However, the nature of proteases produced by basophils has been poorly characterized, particularly in mice. mMCP-11 is the most recently discovered mast cell tryptase in mice and was originally identified as Prss34, which is transcribed in some mast cell-like cell lines and at the early stage in the culture of BMMC with IL-3. Curiously, Prss34 is preferentially expressed in the BM and spleen among normal tissues in contrast to other mast cell tryptases. Therefore, it remains elusive what types of cells express mMCP-11 in vivo. Here, we show that mMCP-11 is highly expressed by primary basophils and to a much lesser extent, by some mast cells. Prss34 transcripts were detected abundantly in primary and cultured basophils and very weakly in peritoneal mast cells or cultured BMMC. Conversely, transcripts for mMCP-6 and mMCP-7 tryptases were preferentially expressed by cultured and peritoneal mast cells but not basophils. We established a mMCP-11-specific mAb and showed that mMCP-11 proteins are indeed expressed by primary basophils and those infiltrating the affected tissues during allergic inflammation and parasitic infections. Some primary mast cells also expressed mMCP-11 proteins, albeit at a much lower level. Thus, basophils rather than mast cells are the major source of mMCP-11. This is the first study to demonstrate that mouse basophils produce a trypsin-like protease. J. Leukoc. Biol. 86: 1417-1425; 2009.