Effects Of Microvascular Endothelial Cells On Neutrophil Bacterial Killing

Background:One of the basic functions of neutrophils is to kill bacteria. However, neutrophils that cross microvascular endothelial cells (MVECs) do not kill invading bacteria, but secrete inflammatory products that can further damage tissue affected by the bacterial infection. This is contrary to the original model of neutrophil transmigration into infected tissue.Objective:However, the mechanism governing this inhibition of neutrophil killing is unknown. To determine whether MVECs are key mediators of neutrophil killing, laying the theoretical foundation for selecting of effective antibacterial Chinese veterinary medicine.Methods:We established a transmigration model using rat intestinal microvascular endothelial cells (RIMVECs) and neutrophils by a system of Transwell, and measured extracellular and intracellular killing of Escherichia coli, Lactobacillus acidophilus, and Staphylococcus aureus in blood and transendothelial neutrophils by colony-count techniques. Matrix metalloproteinase9(MMP-9) concentrations and lysozyme activities of neutrophils were examined by fluorescence microplate reader. Results:1, Blood neutrophils engulf bacteria but do not kill them.2, Lipopolysaccharide-and a-hemolysin-injured RIMVECs caused transendothelial neutrophils to lose extracellular and intracellular bactericidal activity.3, However, transendothelial neutrophils recruited by interleukin-la secreted by RIMVECs effectively killed Gram-positive bacteria.4, LTB4and fMLP+CytB chemotaxis of neutrophils intracellular and extracellular bactericidal effect is obvious.5, It also significantly increased concentrations of MMP-9and lysozyme activities in transendothelial neutrophils (p<0.01and P<0.001, respectively).Conclusion:Our results demonstrate that bactericidal activity of neutrophils requires activation of MVECs, and that the key factor in bacteria-associated inflammation is bacterial toxin damage of MVECs, leading to induction of bactericidal activity of transendothelial neutrophils. Endothelial cells affect neutrophil killing, and that levels of granzyme produced by neutrophils may be increased by activated endothelial cells.