Biological depletion of neutrophils attenuates pro-inflammatory markers and the development of the psoriatic phenotype in a murine model of psoriasis.

Biological depletion of neutrophils attenuates pro-inflammatory markers and the development of the psoriatic phenotype in a murine model of psoriasis.
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DOI:
10.1016/j.clim.2019.108294
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发表时间:
2020-01
期刊:
Clinical immunology (Orlando, Fla.)
影响因子:
--
通讯作者:
Martinez LR
Martinez LR
中科院分区:
其他
文献类型:
--
作者:
Han G;Havnaer A;Lee HH;Carmichael DJ;Martinez LR

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虽然中性粒细胞被认为是银屑病的组织学标志,但其在银屑病中的病理生理作用仍不清楚。我们在小鼠模型中表征了通过注射单克隆抗体1A 8消耗中性粒细胞对咪喹莫特(IMQ)诱导的银屑病病变发展的影响。对病变进行了照片和组织学分析,显示中性粒细胞减少的银屑病样鳞屑和表皮增生减少。ELISA和流式细胞术用于测定细胞因子和免疫细胞的相对水平。与对照组相比,IMQ治疗的血小板减少症小鼠在组织样品中具有显著较低水平的巨噬细胞(P<0.05),并且显示出显著较低数量的CD 4 + T细胞(P<0.05)。中性粒细胞减少组TNF-α、IFN-γ和IL-1β水平低于对照组(P<0.05)。这些结果表明,中性粒细胞减少减少银屑病样皮肤病变的发展,并大大减少促炎细胞因子和免疫细胞浸润IMQ诱导的皮肤病变,表明中性粒细胞在维持银屑病炎症中的积极作用。
Although neutrophils are considered a histologic hallmark of psoriasis, their pathophysiologic role in psoriasis remains unclear. We characterized the effects of neutrophil depletion via injection of monoclonal antibody 1A8 on the development of imiquimod (IMQ)-induced psoriatic lesions in a murine model. Lesions were followed with photographs and histologic analysis, revealing reduced psoriasiform scale and epidermal hyperplasia in neutrophil-depleted. ELISA and flow cytometry were used to determine relative levels of cytokines and immune cells. Compared to controls, IMQ-treated neutropenic mice had significantly lower levels of macrophages in tissue samples (P<0.05) and displayed significantly lower numbers of CD4+ T-cells (P<0.05). Neutropenic animals exhibited lower levels of TNF-α, IFN-γ, and IL-1β than controls (P<0.05). These results show that neutropenia reduces the development of psoriasiform skin lesions and substantially decreases infiltration of pro-inflammatory cytokines and immune cells to IMQ-induced cutaneous lesions, suggesting an active role of neutrophils in maintaining inflammation in psoriasis.
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