Hemin Causes Lung Microvascular Endothelial Barrier Dysfunction by Necroptotic Cell Death.

In this study, we examined whether hemin can cause lung microvascular endothelial barrier dysfunction. By assessing transendothelial resistance using electrical cell impedance sensing, and by directly measuring trans-monolayer FITC-dextran flux, we found that hemin does cause endothelial barrier dysfunction in a concentration-dependent manner. Pre-treatment with either a TLR4 inhibitor, TAK-242, or an antioxidant, N-acetylcysteine, abrogated this effect. Increased monolayer permeability was found to be associated with programmed cell death by necroptosis as evidenced by Trypan blue staining, TUNEL assay, Western blotting for activated forms of key effectors of cell death pathways, and studies utilizing specific inhibitors of necroptosis and apoptosis. Further study examining the role of EC necroptosis in promoting non-cardiogenic pulmonary edema during ACS is warranted, and may open a new avenue of potential treatment for this devastating disease. PMID: 28421813 [PubMed - as supplied by publisher]
Source: American Journal of Respiratory Cell and Molecular Biology - Category: Molecular Biology Authors: Tags: Am J Respir Cell Mol Biol Source Type: research