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

Cell Calcium. 2011 Jul;50(1):54-61. doi: 10.1016/j.ceca.2011.05.002. Epub 2011 May 25.


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 Ca(2+) as an essential player in the signaling cascade by directly inducing Ca(2+) influx using A23187. Elevation of the internal Ca(2+) 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calcimycin / pharmacology
  • Calcium / metabolism*
  • Calcium Signaling
  • Cell Adhesion
  • Erythrocytes / metabolism*
  • Erythrocytes / physiology
  • Humans
  • Lysophospholipids / pharmacology
  • Optical Tweezers


  • Lysophospholipids
  • Calcimycin
  • lysophosphatidic acid
  • Calcium