Reduced CR1 expression on aged human erythrocytes: immuno-electron microscopic and functional analysis

Abstract

Recognition and clearance of aged human erythrocytes (AE) is a complex process involving immune and non-immune reactions. Complement activation on the surface of AE and deposition of the C3b complement component appear to facilitate this process. Complement receptor type 1 (CR1, CD35) expressed on the surface of human erythrocytes binds to C3b molecules and promotes their inactivation by complement factor I. This may protect the erythrocytes from lysis by complement and by phagocytes. It has been previously reported that aging of human erythrocytes is accompanied by a decrease in the number of CR1 molecules expressed on their surface. Results presented here further support this finding with for the first time a presentation of immune-electron microscopic observation. Haemagglutination and binding assays showed that AE express significantly fewer CR1 (CD35) molecules than young erythrocytes (YE). This is associated in AE with reduced CR1-like factor I co-factor activity and increased deposition in vivo of C3, C4 and properdin as well as increased sensitivity to lysis in vitro by homologous and heterologous complement. Three different immuno-electron microscopical techniques have been used to clearly show the quantitative difference in CR1 (CD35) expression between AE and YE. Finally our results demonstrate that the previously reported clustered arrangement of CR1 (CD35) on human erythrocytes is similar on aged and young erythrocytes.