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• W2050872238 abstract "Tumor necrosis factor α (TNF-α) has been reported to be a key component of the functional priming, of both myeloid and nonmyeloid cells, that is thought to contribute to the lung's increased susceptibility to injury following shock. Not surprisingly, we found that mice deficient in TNF-α exhibited reduced acute lung injury (ALI) resultant from the combined insults of hemorrhagic shock and sepsis. However, we found that when we adoptively transferred neutrophils from mice expressing TNF-α to neutrophil-depleted mice that lacked TNF-α, they were not able to serve as priming stimulus for the development of ALI. Based on these findings, we proposed that resident lung tissue cells mediate TNF-α priming. To begin to unravel the complex signaling pathway of various resident lung tissue cells in TNF-α-induced priming, we compared the effect of local (intratracheal [i.t.]) versus systemic [intravenous (i.v.)] delivery of TNF-α small interference (siRNA). We hypothesized that alternately suppressing expression of TNF-α in lung endothelial (i.v.) or epithelial (i.t.) cells would produce a differential effect in shock-induced ALI. We found that when in vivo siRNA i.t. or i.v. against TNF-α was administered to C57/BL6 mice at 2 h after hemorrhage, 24 h before septic challenge, that systemic/i.v., but not i.t., delivery of TNF-α siRNA following hemorrhage priming significantly reduces expression of indices of ALI compared with controls. These findings suggest that an absence of local lung tissue TNF-α significantly reduces lung tissue injury following hemorrhage priming for ALI and that pulmonary endothelial and/or other possible vascular resident cells, not epithelial cells, play a greater role in mediating the TNF-α priming response in a mouse model of hemorrhage/sepsis-induced ALI." @default.
• W2050872238 created "2016-06-24" @default.
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• W2050872238 date "2012-06-01" @default.
• W2050872238 modified "2023-09-26" @default.
• W2050872238 title "The Role and Source of Tumor Necrosis Factor-α in Hemorrhage-Induced Priming for Septic Lung Injury" @default.
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• W2050872238 doi "https://doi.org/10.1097/shk.0b013e318254fa6a" @default.
• W2050872238 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3356491" @default.
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