CR1-mediated ATP Release by Human Red Blood Cells Promotes CR1 Clustering and Modulates the Immune Transfer Process

J Biol Chem. 2013 Oct 25;288(43):31139-53. doi: 10.1074/jbc.M113.486035. Epub 2013 Sep 10.


Humans and other higher primates are unique among mammals in using complement receptor 1 (CR1, CD35) on red blood cells (RBC) to ligate complement-tagged inflammatory particles (immune complexes, apoptotic/necrotic debris, and microbes) in the circulation for quiet transport to the sinusoids of spleen and liver where resident macrophages remove the particles, but allow the RBC to return unharmed to the circulation. This process is called immune-adherence clearance. In this study we found using luminometric- and fluorescence-based methods that ligation of CR1 on human RBC promotes ATP release. Our data show that CR1-mediated ATP release does not depend on Ca(2+) or enzymes previously shown to mediate an increase in membrane deformability promoted by CR1 ligation. Furthermore, ATP release following CR1 ligation increases the mobility of the lipid fraction of RBC membranes, which in turn facilitates CR1 clustering, and thereby enhances the binding avidity of complement-opsonized particles to the RBC CR1. Finally, we have found that RBC-derived ATP has a stimulatory effect on phagocytosis of immune-adherent immune complexes.

Keywords: ATP; CD47; Immune Adherence; MK-571; Neutrophil; Pannexin-1; Phagocytosis; Protein Kinase A (PKA); Protein Kinase C (PKC); Red Blood Cells.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / immunology
  • Adenosine Triphosphate / metabolism*
  • Complement System Proteins / immunology
  • Complement System Proteins / metabolism
  • Erythrocytes / cytology
  • Erythrocytes / immunology
  • Erythrocytes / metabolism*
  • Female
  • Humans
  • Immunologic Capping*
  • Male
  • Membrane Lipids / immunology
  • Membrane Lipids / metabolism
  • Phagocytosis / immunology
  • Receptors, Complement 3b / immunology
  • Receptors, Complement 3b / metabolism*


  • CR1 protein, human
  • Membrane Lipids
  • Receptors, Complement 3b
  • Adenosine Triphosphate
  • Complement System Proteins