品牌：Liposoma

產(chǎn)地：荷蘭

貨號：CP-005-005

規(guī)格：5ml+5ml

品名：Clodronateliposomes & Control Liposomes

代理：靶點科技

部位：肺臟

細(xì)胞：肺泡巨噬細(xì)胞（AM）

劑量：70ul

方式：滴鼻（intratracheal administration）

時間點：建模前48h

題目：Lung-innervating nociceptor sensory neurons promote pneumonic sepsis during carbapenem-resistant Klebsiella pneumoniae lung infection

期刊：SCIENCE ADVANCES

時間：6 Sep 2024

期卷：Vol 10, Issue 36

鏈接：DOI: 10.1126/sciadv.adl6162

摘要：

耐碳青霉烯類肺炎克雷伯菌 （CRKP） 會導(dǎo)致革蘭氏陰性的肺部感染和致命的肺炎膿毒癥，這些疾病的治療選擇有限。肺部由介導(dǎo)呼吸、咳嗽和支氣管收縮的傷害感受器感覺神經(jīng)元密集支配。傷害感受器在防御革蘭氏陰性肺病原體中的作用尚不清楚。在這里，我們發(fā)現(xiàn)肺支配傷害感受器促進(jìn) CRKP 肺炎和肺膿毒癥。小鼠傷害感受器消融可增加肺 CRKP 清除率，抑制 CRKP 的經(jīng)肺泡播散，并保護(hù)小鼠免受體溫過低和死亡。此外，傷害感受器的消融增強了中性粒細(xì)胞和 Ly6Chi 單核細(xì)胞的募集以及細(xì)胞因子誘導(dǎo)。巨噬細(xì)胞清除劑Clodronate Liposomes（liposoma，CP-005-005）清除耗竭小鼠中 Ly6Chi 單核細(xì)胞的耗竭而不是中性粒細(xì)胞的耗竭，肺和肺外 CRKP 清除率降低，表明 Ly6Chi 單核細(xì)胞是調(diào)節(jié)肺膿毒癥的關(guān)鍵細(xì)胞群。此外，神經(jīng)肽降鈣素基因相關(guān)肽抑制 Ly6Chi 單核細(xì)胞中活性氧的誘導(dǎo)及其 CRKP 殺傷能力。靶向傷害感受器信號傳導(dǎo)可能是治療多重耐藥革蘭氏陰性菌感染和肺炎膿毒癥的治療方法。

Abstract:

Carbapenem-resistant Klebsiella pneumoniae (CRKP) causes Gram-negative lung infections and fatal pneumonic sepsis for which limited therapeutic options are available. The lungs are densely innervated by nociceptor sensory neurons that mediate breathing, cough, and bronchoconstriction. The role of nociceptors in defense against Gram-negative lung pathogens is unknown. Here, we found that lung-innervating nociceptors promote CRKP pneumonia and pneumonic sepsis. Ablation of nociceptors in mice increased lung CRKP clearance, suppressed trans-alveolar dissemination of CRKP, and protected mice from hypothermia and death. Furthermore, ablation of nociceptors enhanced the recruitment of neutrophils and Ly6Chi monocytes and cytokine induction. Depletion of Ly6Chi monocytes（liposoma，CP-005-005）, but not of neutrophils, abrogated lung and extrapulmonary CRKP clearance in ablated mice, suggesting that Ly6Chi monocytes are a critical cellular population to regulate pneumonic sepsis. Further, neuropeptide calcitonin gene–related peptide suppressed the induction of reactive oxygen species in Ly6Chi monocytes and their CRKP-killing abilities. Targeting nociceptor signaling could be a therapeutic approach for treating multidrug-resistant Gram-negative infection and pneumonic sepsis.

Liposoma巨噬細(xì)胞清除劑氯膦酸二鈉脂質(zhì)體清除肺泡巨噬細(xì)胞AM：