The impact of alcohol use disorders on pulmonary immune cell inflammatory responses to Streptococcus pneumoniae.
The impact of alcohol use disorders on pulmonary immune cell inflammatory responses to Streptococcus pneumoniae.
复制标题
DOI：
10.1016/j.alcohol.2018.08.016
复制
发表时间：
2019-11
期刊：
影响因子：
--
通讯作者：
Burnham EL
中科院分区：
文献类型：
--
作者：
Gaydos J;McNally A;Burnham EL
由肺炎链球菌引起的社区获得性肺炎通常发生在酒精使用障碍（AUDs）中。AUD患者的肺炎与较差的结局相关，并且不存在缓解这些患者疾病严重程度的特定治疗。许多研究将AUD中肺炎严重程度的增加归因于肺泡巨噬细胞（AM）的异常功能，所述肺泡巨噬细胞是在宿主防御启动中至关重要的肺免疫细胞。没有研究检查人类AM对S的反应。肺炎的AUD。我们推测S.与非AUD参与者相比，AUD参与者的肺炎刺激在数量上有所不同。我们进一步假设，AM炎症介质将减少后，暴露于抗氧化剂，N-乙酰半胱氨酸（NAC）。为了比较，还检查了外周血单核细胞（PBMC）对肺炎球菌蛋白的反应。其他健康的参与者与吸烟匹配的对照组进行支气管肺泡灌洗和外周血采样，以获得AM和PBMC，分别。新鲜收集的细胞与增加剂量的热灭活S. pneumoniae蛋白，有和没有暴露于N-乙酰半胱氨酸。收集细胞培养上清液，并测量炎症介质，包括干扰素（IFN）-γ、白细胞介素（IL）-1β、IL-6和肿瘤坏死因子（TNF）-α。AUDs受试者未受刺激的AM细胞培养上清液中IFN-γ和IL-6显著升高。在用肺炎球菌蛋白刺激后，还观察到AM和PBMC的促炎细胞因子产生的剂量反应性和时间依赖性增加;在AUD和非AUD受试者之间未观察到差异。向肺炎球菌刺激的AM和PBMC中添加NAC通常与细胞因子产生减少相关，但AUD受试者AM培养上清液中的IL-1β除外。我们的观察结果表明，AUDs有助于AM促炎细胞因子产生的基础改变，但不支持肺炎球菌刺激的AM或PBMC炎症介质分泌的一致差异，这些差异与AUDs一致。
Community-acquired pneumonia due to Streptococcus pneumoniae occurs commonly in alcohol use disorders (AUDs). Pneumonia in the AUD patient is associated with poorer outcomes, and specific therapies to mitigate disease severity in these patients do not exist. Numerous investigations have attributed increased severity of pneumonia in AUDs to aberrant function of the alveolar macrophage (AM), a lung immune cell critical in host defense initiation. No studies have examined the response of human AMs to S. pneumoniae in AUDs. We hypothesized that the inflammatory mediators released by AMs after S. pneumoniae stimulation would differ quantitatively in individuals with AUDs compared to non-AUD participants. We further postulated that AM inflammatory mediators would be diminished after exposure to the antioxidant, N-acetylcysteine (NAC). For comparison, responses of peripheral blood mononuclear cells (PBMCs) to pneumococcal protein were also examined. Otherwise healthy participants with AUDs and smoking-matched controls underwent bronchoalveolar lavage and peripheral blood sampling to obtain AMs and PBMCs, respectively. Freshly collected cells were cultured with increasing doses of heat-killed S. pneumoniae protein, with and without exposure to N-acetylcysteine. Cell culture supernatants were collected, and inflammatory mediators were measured, including interferon (IFN)-γ, interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α. IFN-γ and IL-6 were significantly higher in unstimulated AM cell culture supernatants from subjects with AUDs. After stimulation with pneumococcal protein, a dose-response and time-dependent increase in pro-inflammatory cytokine production by both AMs and PBMCs was also observed; differences were not observed between AUD and non-AUD subjects. Addition of NAC to pneumococcal-stimulated AMs and PBMCs was generally associated with diminished cytokine production, with the exception of IL-1β that was elevated in AM culture supernatants from subjects with AUDs. Our observations suggest that AUDs contribute to basal alterations in AM pro-inflammatory cytokine elaboration, but did not support consistent differences in pneumococcal-stimulated AM or PBMC inflammatory mediator secretion that were referable to AUDs.
登录
查看更多内容
DOI：
10.1016/j.bbi.2017.02.014
发表时间：
2017-05
期刊：
Brain, behavior, and immunity
影响因子：
--
作者：
Abdul-Muneer PM;Alikunju S;Mishra V;Schuetz H;Szlachetka AM;Burnham EL;Haorah J
通讯作者：
Haorah J
影响因子：
6.4
作者：
Benin, AL;O'Brien, KL;Whitney, CG
通讯作者：
Whitney, CG
DOI：
10.1152/ajplung.00171.2011
发表时间：
2012-04-01
影响因子：
4.9
作者：
Burnham, Ellen L.;McCord, Joe M.;Gaydos, Jeanette
通讯作者：
Gaydos, Jeanette
影响因子：
1.6
作者：
Beatty JA;Majumdar SR;Tyrrell GJ;Marrie TJ;Eurich DT
通讯作者：
Eurich DT
DOI：
10.1111/j.1530-0277.2010.01259.x
发表时间：
2010-10
期刊：
Alcoholism, clinical and experimental research
影响因子：
--
作者：
Boé DM;Richens TR;Horstmann SA;Burnham EL;Janssen WJ;Henson PM;Moss M;Vandivier RW
通讯作者：
Vandivier RW