CR1-mediated ATP Release by Human Red Blood Cells Promotes CR1 Clustering and Modulates the Immune Transfer Process |
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Authors: | Mark I Melhorn Abigail S Brodsky Jessica Estanislau Joseph A Khoory Ben Illigens Itaru Hamachi Yasutaka Kurishita Andrew D Fraser Anne Nicholson-Weller Elena Dolmatova Heather S Duffy Ionita C Ghiran |
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Institution: | From the ‡Division of Allergy and Inflammation.;the ‖Division of Infectious Diseases.;the **Division of Cardiology.;§Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02115 and ;the ¶Department of Synthetic Chemistry & Biological Chemistry, Graduate School of Engineering, Kyoto University, Katsura, Kyoto 615-8510, Japan |
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Abstract: | 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 Ca2+ 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. |
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Keywords: | ATP Neutrophil Phagocytosis Protein Kinase A (PKA) Protein Kinase C (PKC) CD47 Immune Adherence MK-571 Pannexin-1 Red Blood Cells |
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