title: CR1-mediated ATP release by human red blood cells promotes CR1 clustering and modulates the immune transfer process.
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 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.
authors.affiliation: From the Division of Allergy and Inflammation.
authors.forename: Mark I
authors.initials: MI
authors.lastname: Melhorn
authors.forename: Abigail S
authors.initials: AS
authors.lastname: Brodsky
authors.forename: Jessica
authors.initials: J
authors.lastname: Estanislau
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Khoory
authors.forename: Ben
authors.initials: B
authors.lastname: Illigens
authors.forename: Itaru
authors.initials: I
authors.lastname: Hamachi
authors.forename: Yasutaka
authors.initials: Y
authors.lastname: Kurishita
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Fraser
authors.forename: Anne
authors.initials: A
authors.lastname: Nicholson-Weller
authors.forename: Elena
authors.initials: E
authors.lastname: Dolmatova
authors.forename: Heather S
authors.initials: HS
authors.lastname: Duffy
authors.forename: Ionita C
authors.initials: IC
authors.lastname: Ghiran
mesh_terms: D000255:Adenosine Triphosphate / Q000276:immunology / Q000378:metabolism*; D003165:Complement System Proteins / Q000276:immunology / Q000378:metabolism; D004912:Erythrocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D005260:Female; D006801:Humans; D007152:Immunologic Capping; D008297:Male; D008563:Membrane Lipids / Q000276:immunology / Q000378:metabolism; D010587:Phagocytosis / Q000276:immunology; D017463:Receptors, Complement 3b / Q000276:immunology / Q000378:metabolism*
chemical_list: C509991:CR1 protein, human; D008563:Membrane Lipids; D017463:Receptors, Complement 3b; D000255:Adenosine Triphosphate; D003165:Complement System Proteins
keywords: ATP; CD47; Immune Adherence; MK-571; Neutrophil; Pannexin-1; Phagocytosis; Protein Kinase A (PKA); Protein Kinase C (PKC); Red Blood Cells
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