Sex-dependent acrolein sensitivity in mice is associated with differential lung cell, protein, and transcript changes.
Sex-dependent acrolein sensitivity in mice is associated with differential lung cell, protein, and transcript changes.
复制标题
DOI：
10.14814/phy2.14997
复制
发表时间：
2021-10
影响因子：
2.5
通讯作者：
Leikauf GD
中科院分区：
文献类型：
--
作者：
Bein K;Birru RL;Wells H;Larkin TP;Ge T;Leikauf GD
丙烯醛是一种反应性吸入危害。丙烯醛的初始相互作用本身可以改变功能，随后是复杂的细胞和肺反应的时间依赖性级联反应，这些反应决定了损伤的严重程度。为了研究性别依赖性丙烯醛诱导的急性肺损伤的病理生理学进展，将C57 BL/6 J小鼠暴露于亚致死但有毒和致死的丙烯醛30分钟。雄性小鼠比雌性小鼠更敏感。50 ppm丙烯醛对雌性小鼠亚致死，但对雄性小鼠致死，75 ppm对雌性小鼠致死。致死和亚致死丙烯醛暴露降低支气管肺泡灌洗（BAL）总细胞数在3小时后曝光。细胞数量减少后，总细胞和中性粒细胞数量和蛋白质进行性增加。暴露于亚致死但非致死剂量的雌性小鼠的BAL总细胞数在16 h时恢复至对照水平。与此相反，BAL蛋白含量和中性粒细胞数量更高的小鼠暴露于致死相比，亚致死丙烯醛。RNASeq途径分析发现，雄性小鼠的肺中性粒细胞、谷胱甘肽代谢、氧化应激反应和CCL 7（又名MCP-3）、CXCL 10（又名IP-10）和IL 6转录物的增加幅度大于雌性小鼠，而雌性小鼠的IL-10增加幅度大于雄性小鼠。因此，IL 6：IL 10比率，疾病严重程度的指标，在男性中大于女性。此外，H3.3组蛋白B（H3 F3 B）和前血小板碱性蛋白（PPBP aka CXCL 7）在3 h时在丙烯醛暴露的小鼠BAL和血浆中的转录物增加，而与中性粒细胞胞外陷阱形成相关的H3 F3 B蛋白在12 h时增加。这些结果表明H3 F3 B和PPBP转录本的增加可能有助于细胞外H3 F3 B和PPBP蛋白的增加。为了研究性别依赖性丙烯醛诱导的急性肺损伤的病理生理学进展，将C57 BL/6 J小鼠暴露于致死（75 ppm，图a）和亚致死但有毒（50 ppm，图B）丙烯醛30 min。雄性小鼠比雌性小鼠更敏感。丙烯醛增加小鼠肺中的中性粒细胞、IL 10：IL 6比率和中性粒细胞胞外陷阱蛋白。
Acrolein is a reactive inhalation hazard. Acrolein’s initial interaction, which in itself can be function‐altering, is followed by time‐dependent cascade of complex cellular and pulmonary responses that dictate the severity of the injury. To investigate the pathophysiological progression of sex‐dependent acrolein‐induced acute lung injury, C57BL/6J mice were exposed for 30 min to sublethal, but toxic, and lethal acrolein. Male mice were more sensitive than female mice. Acrolein of 50 ppm was sublethal to female but lethal to male mice, and 75 ppm was lethal to female mice. Lethal and sublethal acrolein exposure decreased bronchoalveolar lavage (BAL) total cell number at 3 h after exposure. The cell number decrease was followed by progressive total cell and neutrophil number and protein increases. The BAL total cell number in female mice exposed to a sublethal, but not lethal dose, returned to control levels at 16 h. In contrast, BAL protein content and neutrophil number were higher in mice exposed to lethal compared to sublethal acrolein. RNASeq pathway analysis identified greater increased lung neutrophil, glutathione metabolism, oxidative stress responses, and CCL7 (aka MCP‐3), CXCL10 (aka IP‐10), and IL6 transcripts in males than females, whereas IL10 increased more in female than male mice. Thus, the IL6:IL10 ratio, an indicator of disease severity, was greater in males than females. Further, H3.3 histone B (H3F3B) and pro‐platelet basic protein (PPBP aka CXCL7), transcripts increased in acrolein exposed mouse BAL and plasma at 3 h, while H3F3B protein that is associated with neutrophil extracellular traps formation increased at 12 h. These results suggest that H3F3B and PPBP transcripts increase may contribute to extracellular H3F3B and PPBP proteins increase. To investigate the pathophysiological progression of sex‐dependent acrolein‐induced acute lung injury, C57BL/6J mice were exposed for 30 min to lethal (75 ppm, Figure a) and sublethal , but toxic (50 ppm, Figure b), acrolein . Male mice were more sensitive than female mice. Acrolein increased neutrophils, IL10:IL6 ratio, and neutrophil extracellular traps proteins in mouse lung.
登录
查看更多内容
组蛋白的杀菌作用。
影响因子：
15.3
作者：
HIRSCH, J G
通讯作者：
HIRSCH, J G
DOI：
10.1164/rccm.201006-0912oc
发表时间：
2011-06-01
影响因子：
24.7
作者：
Leikauf, George D.;Concel, Vincent J.;Prows, Daniel R.
通讯作者：
Prows, Daniel R.
影响因子：
8.8
作者：
Calfee CS;Matthay MA;Kangelaris KN;Siew ED;Janz DR;Bernard GR;May AK;Jacob P;Havel C;Benowitz NL;Ware LB
通讯作者：
Ware LB
影响因子：
3.8
作者：
JAKAB, GJ
通讯作者：
JAKAB, GJ
影响因子：
10.4
作者：
Latoche JD;Ufelle AC;Fazzi F;Ganguly K;Leikauf GD;Fattman CL
通讯作者：
Fattman CL