Role of complement receptor 1 (CR1; CD35) on epithelial cells: A model for understanding complement-mediated damage in the kidney

ABSTRACT Complement-containing immune complexes can be presented to phagocytes by human erythrocytes bearing complement receptor 1 (CR1). Although this has long been assumed to be a mechanism by which humans are able to protect themselves from “extracellular” bacteria such as pneumococci, there is little direct evidence. In these studies we have investigated this question by comparing results for erythrocytes from transgenic mice expressing human CR1 on their erythrocytes to the results for wild-type mouse erythrocytes that do not express CR1. We demonstrate that human CR1 expression on murine erythrocytes allows immune adherence to beads opsonized with either mouse or human serum as a source of complement. The role of CR1 in immune adherence was supported by studies showing that it was blocked by the addition of antibody to human CR1. Furthermore, human CR1 expression enhances the immune adherence of opsonized pneumococci to erythrocytes in vitro, and the pneumococci attached to erythrocytes via CR1 can be transferred in vitro to live macrophages. Even more importantly, we observed that if complement-opsonized pneumococci are injected intravenously with CR1+ mouse erythrocytes into wild-type mice (after a short in vitro incubation), they are cleared faster than opsonized pneumococci similarly injected with wild-type mouse erythrocytes. Finally, we have shown that the intravenous (i.v.) injection of pneumococci into CR1+ mice also results in more rapid blood clearance than in wild-type mice. These data support that immune adherence via CR1 on erythrocytes likely plays an important role in the clearance of opsonized bacteria from human blood.

Download Full-text

SIGNIFICANCE OF COMPLEMENT PROFILE AND COMPLEMENT RECEPTOR 1 EXPRESSION IN RBC AND KIDNEY TISSUE IN IMMUNE COMPLEX MEDIATED DISEASE

Journal of Nepal Medical Association ◽

10.31729/jnma.692 ◽

2003 ◽

Vol 41 (144) ◽

pp. 481-484 ◽

Cited By ~ 1

Author(s):

Nirmal Baral ◽

M Lamsal ◽

L M Shrivastava

Keyword(s):

Immune Complex ◽

Normal Control ◽

Lupus Erythematosus ◽

Kidney Biopsy ◽

Kidney Tissue ◽

Complement Receptor ◽

Type Iv ◽

Appreciable Increase ◽

Complement Receptor 1

A study was conducted to evaluate role of complement proteins and complementreceptor 1 (CR1) in pathogenesis of Systemic lupus erythematosus (SLE) and Immunecomplex (IC) mediated glomerulonephritis. C3, C4, C3d and CH100 in serum, CR1 inrenal biopsies and RBC showed these parameters to be of great diagnostic andprognostic values in Immune complex mediated diseases. Our study revealed an overalldecrease in levels of CR1, C3, C4 in IC mediated as compared to non - IC mediateddisease. Whereas C3d in case of SLE 247 ± 39 AU/L including IC mediatedGlomerulonephritis (ICGN) 208 ± 51 AU/L was found to be significantly increased(P < 0.05) than normal control 46 ± 6 AU/L. There was no appreciable increase incase of non - 1C mediated GN (61 ± 12 AU/L) CRI among SLE patients (261 ± 141/E)and IC mediated group (270 ± 107/E) was found to be significantly lower (P < 0.05)than normal control (627 ± 132/E) and non - IC GN (550 ± 86/E). C4 values amongSLE, patients were found to be 191 ± 104 mg/L as compared to control (286 ±110 mg/L). The kidney biopsy of type III and type IV lupus nephritis revealed a completeabsence of CR1 in contrast to minimal change diseases. Thus this study revealed thatabove parameters could be a valuable tool for distinguishing IC versus non-IC mediatedkidney diseases.Key Words: Complement receptor 1 (CR1) Glomerulonephritis, SLE.

Download Full-text

Complement Receptor 1/Cd35 Is a Receptor for Mannan-Binding Lectin

Journal of Experimental Medicine ◽

10.1084/jem.192.12.1797 ◽

2000 ◽

Vol 192 (12) ◽

pp. 1797-1808 ◽

Cited By ~ 162

Author(s):

Ionita Ghiran ◽

Sergi F. Barbashov ◽

Lloyd B. Klickstein ◽

Sander W. Tas ◽

Jens C. Jensenius ◽

...

Keyword(s):

Cellular Receptor ◽

Carbohydrate Binding ◽

Complement Receptor ◽

Complement Receptor 1 ◽

Complement C1q ◽

Equilibrium Dissociation ◽

Mannan Binding Lectin ◽

Apparent Equilibrium ◽

Binding Lectin

Mannan-binding lectin (MBL), a member of the collectin family, is known to have opsonic function, although identification of its cellular receptor has been elusive. Complement C1q, which is homologous to MBL, binds to complement receptor 1 (CR1/CD35), and thus we investigated whether CR1 also functions as the MBL receptor. Radioiodinated MBL bound to recombinant soluble CR1 (sCR1) that had been immobilized on plastic with an apparent equilibrium dissociation constant of 5 nM. N-acetyl-d-glucosamine did not inhibit sCR1–MBL binding, indicating that the carbohydrate binding site of MBL is not involved in binding CR1. C1q inhibited MBL binding to immobilized sCR1, suggesting that MBL and C1q might bind to the same or adjacent sites on CR1. MBL binding to polymorphonuclear leukocytes (PMNs) was associated positively with changes in CR1 expression induced by phorbol myristate acetate. Finally, CR1 mediated the adhesion of human erythrocytes to immobilized MBL and functioned as a phagocytic receptor on PMNs for MBL–immunoglobulin G opsonized bacteria. Thus, MBL binds to both recombinant sCR1 and cellular CR1, which supports the role of CR1 as a cellular receptor for the collectin MBL.

Download Full-text

Erythrocyte Complement Receptor 1 (ECR1) Gene Polymorphisms and Neonatal Respiratory Distress Syndrome

Journal of Pediatric Genetics ◽

10.1055/s-0040-1717108 ◽

2020 ◽

Author(s):

Walaa Rabie ◽

Ahmed Al-Taweel ◽

Walaa A. Abuelhamd ◽

Walaa Shahin ◽

Marian Nazeer ◽

...

Keyword(s):

Respiratory Distress Syndrome ◽

Respiratory Distress ◽

Gene Polymorphisms ◽

Distress Syndrome ◽

Complement Receptor ◽

Allelic Discrimination ◽

Single Nucleotide ◽

Complement Receptor 1 ◽

Polymerase Chain

AbstractTo evaluate the role of erythrocyte complement receptor 1 (ECR1) gene in the predisposition to respiratory distress syndrome (RDS), we studied 50 infants with RDS and 50 controls. Real-time polymerase chain reaction allelic discrimination analysis of A3650G (rs2274567) and genotyping of the alleles (HindIII) were performed. Allele L of HindIII restricted single nucleotide polymorphism (SNP) associated with the severity of RDS. Duration of oxygen and ventilation in genotypes AA and AG of A3650G SNP was longer than genotype GG (17.6 ± 19.4 and 8.6 ± 4.5 days, p = 0.01) and (8.9 ± 11.9 and 3.9 ± 3.53 days, p = 0.03), respectively. A3650G and HINDIII digested gene polymorphisms of ECR1 may be of little importance for RDS.

Download Full-text