近日，德国马格德堡大学Anne Dudeck课题组发现，肥大细胞来源的肿瘤坏死因子可促进中性粒细胞的血管外渗。2021年1月22日，《免疫》杂志在线发表了这项成果。

研究人员发现，肥大细胞（MC）来源的肿瘤坏死因子（TNF）通过促进管腔内爬行，对于嗜中性白细胞向接触性超敏反应诱发的皮肤炎症部位的渗出至关重要。MC来源的TNF可通过TNF受体1（TNFR1）直接引发循环中性粒细胞，而可用于内皮细胞活化。通过将血管周围MC定向脱粒，MC来源的TNF被注入血液；这些血管周围MC是血管单元的一部分，可进入血管腔。一致地，静脉内注射MC颗粒可促进中性粒细胞的外渗。

在IgE交联或LPs攻击后，研究人员还观察到明显且迅速的血管内MC脱粒现象，这表明了普遍的MC潜力。因此，促炎性介质进入血流的定向MC脱粒可能是减轻细胞因子风暴综合征或休克症状或增强免疫防御的治疗靶标。

据悉，组织常驻MC在发炎时会迅速引发嗜中性粒细胞浸润，但分子机制仍是未知的。

附：英文原文

Title: Directional mast cell degranulation of tumor necrosis factor into blood vessels primes neutrophil extravasation

Author: Jan Dudeck, Johanna Kotrba, Roland Immler, Aaron Hoffmann, Martin Voss, Vasileia Ismini Alexaki, Lorena Morton, Stephan René Jahn, Konstantinos Katsoulis-Dimitriou, Simon Winzer, Georg Kollias, Thomas Fischer, Sergei A. Nedospasov, Ildiko Rita Dunay, Triantafyllos Chavakis, Andreas J. Müller, Burkhart Schraven, Markus Sperandio, Anne Dudeck

Issue&Volume: 2021-01-22

Abstract: Tissue resident mast cells (MCs) rapidly initiate neutrophil infiltration upon inflammatoryinsult, yet the molecular mechanism is still unknown. Here, we demonstrated that MC-derivedtumor necrosis factor (TNF) was crucial for neutrophil extravasation to sites of contacthypersensitivity-induced skin inflammation by promoting intraluminal crawling. MC-derivedTNF directly primed circulating neutrophils via TNF receptor-1 (TNFR1) while beingdispensable for endothelial cell activation. The MC-derived TNF was infused into thebloodstream by directional degranulation of perivascular MCs that were part of thevascular unit with access to the vessel lumen. Consistently, intravenous administrationof MC granules boosted neutrophil extravasation. Pronounced and rapid intravascularMC degranulation was also observed upon IgE crosslinking or LPs challenge indicatinga universal MC potential. Consequently, the directional MC degranulation of pro-inflammatorymediators into the bloodstream may represent an important target for therapeutic approachesaimed at dampening cytokine storm syndromes or shock symptoms, or intentionally pushingimmune defense.

DOI: 10.1016/j.immuni.2020.12.017

Source: https://www.cell.com/immunity/fulltext/S1074-7613(20)30545-8