title: Ligation of complement receptor 1 increases erythrocyte membrane deformability.
abstract: Microbes as well as immune complexes and other continuously generated inflammatory particles are efficiently removed from the human circulation by red blood cells (RBCs) through a process called immune-adherence clearance. During this process, RBCs use complement receptor 1 (CR1, CD35) to bind circulating complement-opsonized particles and transfer them to resident macrophages in the liver and spleen for removal. We here show that ligation of RBC CR1 by antibody and complement-opsonized particles induces a transient Ca(++) influx that is proportional to the RBC CR1 levels and is inhibited by T1E3 pAb, a specific inhibitor of TRPC1 channels. The CR1-elicited RBC Ca(++) influx is accompanied by an increase in RBC membrane deformability that positively correlates with the number of preexisting CR1 molecules on RBC membranes. Biochemically, ligation of RBC CR1 causes a significant increase in phosphorylation levels of β-spectrin that is inhibited by preincubation of RBCs with DMAT, a specific casein kinase II inhibitor. We hypothesize that the CR1-dependent increase in membrane deformability could be relevant for facilitating the transfer of CR1-bound particles from the RBCs to the hepatic and splenic phagocytes.
authors.affiliation: Division of Allergy and Inflammation, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Aleksandra M
authors.initials: AM
authors.lastname: Glodek
authors.forename: Rossen
authors.initials: R
authors.lastname: Mirchev
authors.forename: David E
authors.initials: DE
authors.lastname: Golan
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Khoory
authors.forename: Jennie M
authors.initials: JM
authors.lastname: Burns
authors.forename: Sergey S
authors.initials: SS
authors.lastname: Shevkoplyas
authors.forename: Anne
authors.initials: A
authors.lastname: Nicholson-Weller
authors.forename: Ionita C
authors.initials: IC
authors.lastname: Ghiran
mesh_terms: D002118:Calcium / Q000378:metabolism; D002148:Calmodulin-Binding Proteins / Q000378:metabolism; D047390:Casein Kinase II / Q000037:antagonists & inhibitors / Q000378:metabolism; D004906:Erythrocyte Count; D004910:Erythrocyte Membrane / Q000378:metabolism* / Q000473:pathology*; D005434:Flow Cytometry; D006801:Humans; D008264:Macrophages / Q000378:metabolism / Q000473:pathology*; D010587:Phagocytosis; D010766:Phosphorylation; D011951:Receptors, Complement / Q000378:metabolism*; D013049:Spectrin / Q000378:metabolism; D050052:TRPC Cation Channels / Q000378:metabolism; D000099291:Adducins
chemical_list: D002118:Calcium; D002148:Calmodulin-Binding Proteins; D047390:Casein Kinase II; D011951:Receptors, Complement; D013049:Spectrin; D050052:TRPC Cation Channels; D000099291:Adducins; C096351:transient receptor potential cation channel, subfamily C, member 1