Mitochondrial DNA Activates Endothelium Cells To Cause Acute Lung Injury

Object The present study was performed to:(1) observe effects of mitochondrial DNA on activation and permeability of micro vascular endothelium cells in rats and investigate its molecular biological mechanism.(2) To provide the experimental basis on the treatment of post-traumatic SIRS and acute lung injury.Methods Using mtDNA of Clinical concentrations by the rat tail vein injection gave rise to SIRS/ALI and inflammatory factor TNF-α, IL-6and sE-selectin, sICAM-1activation markers of endothelial cells in peripheral blood circulation and also pulmonary vascular permeability with Evans Blue staining method were examined. Pulmonary microvascular endothelium cells (PMECs) were harvested from male SD rats by tissue-sticking method and then cultured. Monolayer PMECs were established in upper room of24-well Transwell plate to investigate permeability and viability of PMECs after mtDNA stimulation and drug treatments, adhesion of polymorphonuclear neutrophils to PMECs. the expression of NF-κB subunit p65mRNA, I-κB mRNA and TLR-9mRNA were analyzed by Real-time PCRResults mtDNA (lOug/ml) could activate NF-κB pathway in Pulmonary microvascular endothelium cells through TLR9, upgrade the expression of TLR-9mRNA, p65mRNA and I-KBmRNA, increase permeability of pulmonary microvascular endothelium cells, Significantly improve adhesion of polymorphonuclear neutrophils to PMECs.Conclusions mtDNA of SD rat could activate endothelial cells and promotes neutrophil adherence through TLR9signaling and NF-κB pathway. mtDNA of SD rat could activate pulmonary microvascular endothelium cells, increase permeability of pulmonary microvascular endothelium cells, Significantly improve adhesion of polymorphonuclear neutrophils to PMECs.