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Key role of the number of complement receptor 1 on erythrocytes for binding of Escherichia coli to erythrocytes and for leukocyte phagocytosis and oxidative burst in human whole blood

Brekke, Ole-Lars; Christiansen, Dorte; Kisserli, Aymric; Fure, Hilde; Dahl, Jim André; Donvito, Béatrice; Reveil, Brigitte; Ludviksen, Judith K; Tabary, Thierry; Mollnes, Tom Eirik; Cohen, Jacques H.M.
Journal article; SubmittedVersion
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artikkel380.pdf (1.048Mb)
Year
2019
Permanent link
http://urn.nb.no/URN:NBN:no-78529

CRIStin
1722749

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  • Institutt for klinisk medisin [5298]
  • CRIStin høstingsarkiv [14985]
Original version
Molecular Immunology. 2019, 114, 139-148, DOI: https://doi.org/10.1016/j.molimm.2019.07.014
Abstract
Aim

To study the role of complement receptor 1 (CR1) for binding of Escherichia coli (E. coli) to erythrocytes, for leukocyte phagocytosis, oxidative burst and complement activation in human whole blood from a CR1 deficient (CR1D) patient and healthy controls with low, medium and high CR1 numbers.

Methods

Alexa-labelled bacteria were used to quantify erythrocyte-bound bacteria, free bacteria in plasma and phagocytosis using flow cytometry. Complement activation in plasma was measured by enzyme-linked immunosorbent assay. The CR1 numbers as well as C3bc and C4bc deposition on erythrocytes were measured by flow cytometry. Cytokines were measured using multiplex technology, and bacterial growth was measured by colony forming units. CR1 was blocked using the anti-CR1 blocking mAb 3D9.

Results

Approximately 85% of E. coli bound to erythrocytes after 15 min incubation in donor blood with high and medium CR1 numbers, 50% in the person with low CR1 numbers and virtually no detectable binding in the CR1D (r2 = 0.87, P < 0.0007). The number of free bacteria in plasma was inversely related to erythrocyte CR1 numbers (r2 = 0.98, P < 0.0001). E. coli-induced phagocytosis and oxidative burst were significantly enhanced by the anti-CR1 mAb 3D9 and in the CR1D and the donor with low CR1 numbers. E. coli-induced complement activation in plasma, C3bc and C4bc deposition on erythrocytes, and bacterial growth were similar in all four cases.

Conclusions

CR1D and low CR1 numbers prevented E. coli binding to erythrocytes, increased free bacteria in plasma, phagocytosis and oxidative burst, but did not affect plasma or surface complement activation and bacterial growth.
 
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