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

TL;DR

This study demonstrates that stimulation of human red blood cells with LPA or Ca2+ influx induces irreversible intercellular adhesion, suggesting a role in blood clot formation and pathological conditions like sickle cell crises.

Contribution

It provides experimental evidence that Ca2+-mediated signaling induces RBC adhesion, highlighting a novel mechanism in thrombus solidification.

Findings

LPA induces irreversible RBC adhesion.

Ca2+ influx is essential for RBC adhesion.

Adhesion force is approximately 100 pN.

Abstract

Red 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 tweezers 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 pN, 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.