Stimulation of human red blood cells leads to Ca2+-mediated intercellular adhesion

Abstract

AbstractRed blood cells (RBCs) are a major component of blood clots, which form physiologically as a response to injury or pathologically in thrombosis. The active participation of RBCs in thrombus solidification has been previously proposed but not yet experimentally proven. Holographic optical tweezer s and single-cell force spectroscopy were used to study potential cell– cell adhesion between RBCs. Irreversible intercellular adhesion of RBCs could be induced by stimulation with lysophosphatidic acid (LPA), a compound known to be released by activated platelets. We identified Ca2+ as an essential player in the signaling cascade by directly inducing Ca2+ influx using A23187. Elevation of the internal Ca2+ concentration leads to an intercellular adhesion of RBCs similar to that induced by LPA stimulation. Using single-cell force spectroscopy, the adhesion of the RBCs was identified to be approximately 100 p N, a value large enough to be of significance inside a blood clot or in pathological situations like the vasco-occlusive crisis in sickle cell disease patients.KeywordsIntercellular AdhesionLysophosphatidic AcidMicrofluidic ChamberA23187 StimulationAnnexin Binding BufferThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.