RESUMEN
INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Asunto(s)
Hemorragia/inmunología , Lesión Pulmonar/inmunología , Pulmón/inmunología , Células Mieloides/inmunología , Receptores Toll-Like/inmunología , Heridas y Lesiones/inmunología , Animales , Hemorragia/complicaciones , Interleucina-10/inmunología , Lesión Pulmonar/etiología , Masculino , Ratones , Factor de Necrosis Tumoral alfa/inmunología , Heridas y Lesiones/complicacionesRESUMEN
ABSTRACT: Myeloid-derived suppressor cells (MDSCs) are a heterogenous population of immature myeloid cells hallmarked by their potent immunosuppressive function in a vast array of pathologic conditions. MDSCs have recently been shown to exhibit marked expansion in acute inflammatory states including traumatic injury, burn, and sepsis. Although MDSCs have been well characterized in cancer, there are significant gaps in our knowledge of their functionality in trauma and sepsis, and their clinical significance remains unclear. It is suggested that MDSCs serve an important role in quelling profound inflammatory responses in the acute setting; however, MDSC accumulation may also predispose patients to developing persistent immune dysregulation with increased risk for nosocomial infections, sepsis, and multiorgan failure. Whether MDSCs may serve as the target for novel therapeutics or an important biomarker in trauma and sepsis is yet to be determined. In this review, we will discuss the current understanding of MDSCs within the context of specific traumatic injury types and sepsis. To improve delineation of their functional role, we propose a systemic approach to MDSC analysis including phenotypic standardization, longitudinal analysis, and expansion of clinical research.