Indolic Uremic Solutes Enhance Procoagulant Activity of Red Blood Cells through Phosphatidylserine Exposure and Microparticle Release

Microparticle
DOI: 10.3390/toxins7114390 Publication Date: 2015-10-28T17:43:01Z
ABSTRACT
Increased accumulation of indolic uremic solutes in the blood patients contributes to risk thrombotic events. Red cells (RBCs), most abundant circulation, may be a privileged target these solutes. However, effect indoxyl sulfate (IS) and indole-3-acetic acid (IAA) on procoagulant activity (PCA) erythrocyte is unclear. Here, RBCs from healthy adults were treated with IS IAA (mean maximal concentrations reported patients). Phosphatidylserine (PS) exposure their microparticles (MPs) release labeled Alexa Fluor 488-lactadherin detected by flow cytometer. Cytosolic Ca(2+) ([Ca(2+)]) Fluo 3/AM was analyzed PCA assessed clotting time purified coagulation complex assays. We found that PS exposure, MPs generation, consequent at mean enhanced peaked concentrations. Moreover, 128 nM lactadherin, inhibitor, inhibited over 90% RMPs. Eryptosis or damage, due to, least partially, increase cytosolic [Ca(2+)]. Our results suggest RBC eryptosis plays an important role thrombus formation through releasing RMPs exposing PS. Lactadherin acts as efficient anticoagulant this process.
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