Wohlsein Jan C, Meurer Marita, Neßler Jasmin, Wohlsein Peter, von Köckritz-Blickwede Maren, Baumgärtner Wolfgang, Tipold Andrea
Department of Small Animal Medicine and Surgery, University of Veterinary Medicine Hannover, Foundation, Hannover, Germany.
Department of Biochemistry, University of Veterinary Medicine Hannover, Foundation, Hannover, Germany.
Front Vet Sci. 2022 May 3;9:863579. doi: 10.3389/fvets.2022.863579. eCollection 2022.
Extracellular traps (ETs) are DNA networks formed by immune cells to fight infectious diseases by catching and attacking pathogenic microorganisms. Uncontrolled ET formation or impaired ET clearance can cause tissue and organ damage. Steroid-responsive meningitis-arteritis (SRMA) represents an immune-mediated, presumably non-infectious, purulent leptomeningitis and fibrinoid-necrotizing arteritis and periarteritis of young-adult dogs. Chronic and recurrent cases of SRMA are characterized by lymphohistiocytic inflammatory cell infiltration in the meninges and perivascular tissue. This study aimed to identify extracellular traps in dogs with SRMA, a model for immune-mediated diseases in the central nervous system (CNS). Hematoxylin and eosin-stained samples of two young dogs with chronic, recurrent SRMA were examined by light microscopy for characteristic lesions and consecutive slices of affected tissues were stained for detection of ETs by immunofluorescence microscopy using antibodies against DNA-histone-1 complexes, myeloperoxidase, and citrullinated histone H3. Histology revealed purulent and lymphohistiocytic leptomeningitis ( = 2/2) with meningeal periarteritis ( = 2/2) and periadrenal located lymphohistiocytic periarteritis ( = 1). Extracellular DNA networks and inflammatory cell infiltrates of macrophages, neutrophil granulocytes, and lymphocytes were detected in the subarachnoid space of the leptomeninx ( = 2/2) and perivascularly in meningeal ( = 2/2) as well as periadrenal vessels ( = 1/1). In summary, extracellular DNA fibers and attached ET markers are detectable in affected perivascular and meningeal tissues of dogs suffering from SRMA. The proof of principle could be confirmed that ETs are present in canine, inflammatory, and non-infectious CNS diseases and possibly play a role in the pathogenesis of SRMA.
细胞外陷阱（ETs）是免疫细胞形成的DNA网络，通过捕获和攻击病原微生物来对抗传染病。不受控制的ET形成或ET清除受损会导致组织和器官损伤。类固醇反应性脑膜炎动脉炎（SRMA）是一种免疫介导的、可能非感染性的化脓性软脑膜炎以及年轻成年犬的纤维蛋白样坏死性动脉炎和动脉周围炎。SRMA的慢性和复发病例的特征是脑膜和血管周围组织中有淋巴细胞组织细胞性炎性细胞浸润。本研究旨在鉴定患有SRMA的犬（一种中枢神经系统（CNS）免疫介导疾病的模型）中的细胞外陷阱。对两只患有慢性复发性SRMA的幼犬的苏木精和伊红染色样本进行光学显微镜检查以观察特征性病变，并对受影响组织的连续切片进行染色，使用抗DNA-组蛋白-1复合物、髓过氧化物酶和瓜氨酸化组蛋白H3的抗体通过免疫荧光显微镜检测ETs。组织学显示化脓性和淋巴细胞组织细胞性软脑膜炎（2/2）伴脑膜动脉周围炎（2/2）和肾上腺周围淋巴细胞组织细胞性动脉周围炎（1）。在软脑膜的蛛网膜下腔（2/2）以及脑膜（2/2）和肾上腺周围血管（1/1）的血管周围检测到细胞外DNA网络以及巨噬细胞、中性粒细胞和淋巴细胞的炎性细胞浸润。总之，在患有SRMA的犬的受影响血管周围和脑膜组织中可检测到细胞外DNA纤维和附着的ET标记物。原则证明得以确认，即ETs存在于犬类炎性和非感染性CNS疾病中，并且可能在SRMA的发病机制中起作用。
