Rani Meenakshi, Sayyadioskoie Shannon R, Galvan Eva M, Nicholson Susannah E, Schwacha Martin G
Department of Surgery, Division of Trauma and Emergency Surgery, The University of Texas Health Science Center at San Antonio, San Antonio, TX, United States.
Department of Surgery, Division of Trauma and Emergency Surgery, The University of Texas Health Science Center at San Antonio, San Antonio, TX, United States.
Cytokine. 2021 May;141:155457. doi: 10.1016/j.cyto.2021.155457. Epub 2021 Feb 10.
Traumatic injury with hemorrhage (TH) induces an inflammatory response in the lung resulting in lung injury involving activation of immune cells including myeloid cells (i.e., monocytes, granulocytes and macrophages), in part through TLRs. TLRs, via the recognition of damage associated molecular patterns (DAMPs), are a key link between tissue injury and inflammation. Nonetheless, the role of TLRs in myeloid cell activation and TH-induced lung injury remains ill defined.
C57BL/6 male mice were subjected to TH or sham treatment (n = 4-6 /group). Lung tissues were collected two hrs. after injury. Single cells were isolated from the lungs by enzymatic digestion and myeloid cell TLR expression and activation (i.e., cytokine production) were assessed using flow cytometry techniques.
The injury was associated with a profound change in the lung myeloid cell population. TH markedly increased lung CD11b monocyte numbers and Gr1 granulocyte numbers as compared to sham mice. The number of cells expressing TLR2, TLR4, and TLR9 were increased 4-7 fold in the TH mice. Activation for elevated cytokine (TNFα, IL-10) production was observed in the lung monocyte population of the TH mice.
Trauma-induced lung injury is associated with infiltration of the lungs with TLR expressing myeloid cells that are activated for elevated cytokine responses. This elevation in TLR expression may contribute to DAMP-mediated pulmonary complications of an inflammatory nature and warrants further investigation.
创伤性出血(TH)会引发肺部炎症反应,导致肺损伤,部分是通过Toll样受体(TLR)激活包括髓样细胞(即单核细胞、粒细胞和巨噬细胞)在内的免疫细胞。TLR通过识别损伤相关分子模式(DAMP),是组织损伤与炎症之间的关键环节。然而,TLR在髓样细胞激活和TH诱导的肺损伤中的作用仍不明确。
将C57BL/6雄性小鼠进行TH或假手术处理(每组n = 4 - 6只)。损伤后两小时收集肺组织。通过酶消化从肺中分离单个细胞,并使用流式细胞术技术评估髓样细胞TLR表达和激活情况(即细胞因子产生)。
损伤与肺髓样细胞群体的深刻变化有关。与假手术小鼠相比,TH显著增加了肺中CD11b单核细胞数量和Gr1粒细胞数量。TH小鼠中表达TLR2、TLR4和TLR9的细胞数量增加了4 - 7倍。在TH小鼠的肺单核细胞群体中观察到细胞因子(TNFα、IL - 10)产生增加的激活情况。
创伤诱导的肺损伤与表达TLR的髓样细胞浸润肺有关,这些细胞被激活以产生升高的细胞因子反应。TLR表达的这种升高可能导致DAMP介导的炎症性肺部并发症,值得进一步研究。