Division of Infection Medicine, Department of Clinical Sciences Lund, Lund University, Lund, Sweden;
Department of Pediatrics and.
Blood. 2015 Oct 29;126(18):2128-37. doi: 10.1182/blood-2015-04-641142. Epub 2015 Aug 4.
Neutrophils are essential for host defense at the oral mucosa and neutropenia or functional neutrophil defects lead to disordered oral homeostasis. We found that neutrophils from the oral mucosa harvested from morning saliva had released neutrophil extracellular traps (undergone NETosis) in vivo. The NETosis was mediated through intracellular signals elicited by binding of sialyl Lewis(X) present on salival mucins to l-selectin on neutrophils. This led to rapid loss of nuclear membrane and intracellular release of granule proteins with subsequent neutrophil extracellular trap (NET) release independent of elastase and reduced NAD phosphate-oxidase activation. The saliva-induced NETs were more DNase-resistant and had higher capacity to bind and kill bacteria than NETs induced by bacteria or by phorbol-myristate acetate. Furthermore, saliva/sialyl Lewis(X) mediated signaling enhanced intracellular killing of bacteria by neutrophils. Saliva from patients with aphthous ulcers and Behçet disease prone to oral ulcers failed to induce NETosis, but for different reasons it demonstrated that disordered homeostasis in the oral cavity may result in deficient saliva-mediated NETosis.
中性粒细胞对于口腔黏膜的宿主防御至关重要，而中性粒细胞减少或功能中性粒细胞缺陷会导致口腔稳态失调。我们发现，从清晨唾液中采集的口腔黏膜中的中性粒细胞已经在体内发生了中性粒细胞胞外诱捕（NETosis）。这种 NETosis 是通过唾液粘蛋白上存在的唾液酸化 Lewis(X)与中性粒细胞上的 l-选择素结合，引发细胞内信号而介导的。这导致核膜迅速丧失，细胞内颗粒蛋白释放，随后中性粒细胞胞外陷阱（NET）释放，不依赖于弹性蛋白酶，并且 NAD 磷酸氧化酶的激活减少。唾液诱导的 NET 比细菌或佛波醇肉豆蔻酸乙酯诱导的 NET 具有更高的 DNase 抗性和结合并杀死细菌的能力。此外，唾液/唾液酸化 Lewis(X)介导的信号增强了中性粒细胞对细菌的细胞内杀伤。复发性口疮溃疡和易发生口腔溃疡的贝切特病患者的唾液未能诱导 NETosis，但由于不同的原因表明，口腔内的稳态失调可能导致唾液介导的 NETosis 不足。
