During hemolysis, hemoglobin and heme released from red blood cells promote oxidative stress, inflammation and thrombosis. Plasma haptoglobin and hemopexin scavenge free hemoglobin and heme, respectively, but can be depleted in hemolytic states. Haptoglobin and hemopexin supplementation protect tissues, including the vasculature, liver and kidneys. It is widely assumed that these protective effects are due primarily to hemoglobin and heme clearance from the vasculature. However, this simple assumption does not account for the consequent cytoprotective adaptation seen in cells and organs. To further address the mechanism, we used a hyperhemolytic murine model (Townes-SS) of sickle cell disease to examine cellular responses to haptoglobin and hemopexin supplementation. A single infusion of haptoglobin or hemopexin (± equimolar hemoglobin) in SS-mice increased heme oxygenase-1 (HO-1) in the liver, kidney and skin several fold within 1 hour and decreased nuclear NF-ĸB phospho-p65, and vaso-occlusion for 48 hours after infusion. Plasma hemoglobin and heme levels were not significantly changed 1 hour after infusion of haptoglobin or hemopexin. Haptoglobin and hemopexin also inhibited hypoxia/reoxygenation and lipopolysaccharide-induced vaso-occlusion in SS-mice. Inhibition of HO-1 activity with tin protoporphyrin blocked the protections afforded by haptoglobin and hemopexin in SS-mice. The HO-1 reaction product carbon monoxide, fully restored the protection, in part by inhibiting Weibel-Palade body mobilization of P-selectin and von Willebrand factor to endothelial cell surfaces. Thus, the mechanism by which haptoglobin and hemopexin supplementation in hyperhemolytic SS-mice induces cytoprotective cellular responses is linked to increased HO-1 activity.
Pubmed ID: 29694434 RIS Download
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View all literature mentionsConfocal microscopy can improve conventional fluorescence images by recording fluorescence generated from the focal plane within the sample, while rejecting all other light coming from above or below the focal plane. The efficient point-scan/pinhole-detection confocal optics of the FluoView systems virtually eliminate out of focus light to produce high-contrast images with superb resolution. The FluoView systems are fully integrated workstations that incorporate user-friendly image acquisition and image analysis software with high-resolution confocal optics that require no user alignment. An , Windows-based graphic user interface allows new users to quickly generate images in various scan modes, such as XY, XZ, XT, XYZ, XYT, and XYZT. Standard image formats, including TIFF and AVI, permit easy, direct export of FluoView images to off-line analysis packages. XY scanning is performed with a pair of galvanometric mirrors, yielding a wide scanning range to cover up to a field number of 20. The optical zoom (up to 10x magnification) can be performed by narrowing the scanning range while maintaining the maximum pixel resolution of up to 2048 x 2048 pixels.
View all literature mentionsConfocal microscopy can improve conventional fluorescence images by recording fluorescence generated from the focal plane within the sample, while rejecting all other light coming from above or below the focal plane. The efficient point-scan/pinhole-detection confocal optics of the FluoView systems virtually eliminate out of focus light to produce high-contrast images with superb resolution. The FluoView systems are fully integrated workstations that incorporate user-friendly image acquisition and image analysis software with high-resolution confocal optics that require no user alignment. An , Windows-based graphic user interface allows new users to quickly generate images in various scan modes, such as XY, XZ, XT, XYZ, XYT, and XYZT. Standard image formats, including TIFF and AVI, permit easy, direct export of FluoView images to off-line analysis packages. XY scanning is performed with a pair of galvanometric mirrors, yielding a wide scanning range to cover up to a field number of 20. The optical zoom (up to 10x magnification) can be performed by narrowing the scanning range while maintaining the maximum pixel resolution of up to 2048 x 2048 pixels.
View all literature mentionsCell line HUVEC-C is a Finite cell line with a species of origin Homo sapiens
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