How neutrophils (polymorphonuclear neutrophils, PMNs) damage vessels in leukocytoclastic vasculitis (LcV) mediated by immune complexes (ICs) is unclear. If degradative enzymes and oxygen radicals are released from PMNs while adhering to the inner side of the vessel wall, they could be washed away by the blood stream or neutralized by serum protease inhibitors. We investigated if in LcV PMNs could damage vessels from the tissue side after transmigration. We used CD18-deficient (CD18-/-) mice because the absence of CD18 excludes transmigration of PMNs. When eliciting the Arthus reaction in ears of CD18-/- mice, deposition of ICs was not sufficient to recruit PMNs or to induce IC-mediated LcV. Injection of PMNs intradermally in CD18-/- mice allowed us to investigate if bypassing diapedesis and placing PMNs exclusively on the abluminal side leads to vascular destruction. We found that injected PMNs gathered around perivascular ICs, but did not cause vessel damage. Only intravenous injection of wild-type PMNs could re-establish the Arthus reaction in CD18-/- mice. Thus, PMNs cause vessel damage during diapedesis from the luminal side, but not from the perivascular space. We suggest that in order to shield the cytotoxic products from the blood stream, ICs induce particularly tight interactions between them, PMNs and endothelial cells.

译文

中性粒细胞 (多形核中性粒细胞,PMNs) 如何损害由免疫复合物 (ICs) 介导的白细胞碎裂血管炎 (LcV) 中的血管尚不清楚。如果降解酶和氧自由基从pmn中释放出来,同时粘附在血管壁的内侧,则它们可能会被血流冲走或被血清蛋白酶抑制剂中和。我们调查了在LcV中,pmn是否会在迁移后从组织侧损坏血管。我们使用CD18-deficient (CD18-/-) 小鼠,因为缺少CD18排除了pmn的迁移。当在CD18-/-小鼠的耳朵中引起Arthus反应时,ICs的沉积不足以募集pmn或诱导IC介导的LcV。在CD18-/-小鼠中皮内注射pmn使我们能够研究是否绕过血管造影并仅将pmn放置在管腔侧会导致血管破坏。我们发现注射的pmn聚集在血管周围ICs周围,但不会引起血管损伤。只有静脉注射野生型PMNs才能在CD18-/-小鼠中重新建立Arthus反应。因此,pmn在从管腔侧 (而不是从血管周围空间) 进行的排尿过程中会引起血管损伤。我们建议,为了从血流中屏蔽细胞毒性产物,ICs在它们,pmn和内皮细胞之间诱导特别紧密的相互作用。

+1
+2
100研值 100研值 ¥99课程
检索文献一次
下载文献一次

去下载>

成功解锁2个技能,为你点赞

《SCI写作十大必备语法》
解决你的SCI语法难题!

技能熟练度+1

视频课《玩转文献检索》
让你成为检索达人!

恭喜完成新手挑战

手机微信扫一扫,添加好友领取

免费领《Endnote文献管理工具+教程》

微信扫码, 免费领取

手机登录

获取验证码
登录