Uptake of recombinant myeloperoxidase, free or fused to Fcy, by macrophages enhances killing activity toward micro-organisms

Tournay C., Courtoy P.J., Marodi L., Totté Philippe, Wérenne John, Jacquet A., Garcia Quintana L., Bollen A., Moguilevsky N.. 1996. Uptake of recombinant myeloperoxidase, free or fused to Fcy, by macrophages enhances killing activity toward micro-organisms. DNA and Cell Biology, 15 (8) : 617-624.

Autre titre : La capture par les macrophages de myéloperoxidase, libre ou fusionnée au Fcy augmente leur activité microbicide

Résumé : A chimeric antibody-like molecule consisting of the human myeloperoxidase (rMPO) fused to the second and third constant-sequence (CH2 and CH3) Fc domains of human immunoglobulin G-I has been constructed and expressed in Chinese hamster ovary (CHO) cells. This fusion molecule was designed to combine the binding specificity of Fc with the antimicrobial properties of rMPO. The rMPO-Fc fusion dimerized through the Fc fragment, while retaining the enzymatic activity of rMPO. The chimeric molecule was glycosylated and most of the propeptide was eliminated, indicating a better processing of the polypeptide than for rMPO alone. Both rMPO and rMPO-Fc bound to and were internalized by macrophage-like U937 promonocytic cells. Unexpectedly, the chimera failed to bind to the Fc receptor but interacted with a higher affinity than rMPO with the same binding sites. The presence of the Fc fragment in the chimera, in addition, did not extend the plasma half-life of the fusion protein. In vitro, rMPO-Fc exhibited stronger killing effect than rMPO toward Candida albicans in the presence of either H2O2 lone or human macrophages. #In viva#, rMPO-Fc similarly conferred a better protection than rMPO in a lethal model of murine cowdriosis. These properties could be related to the c-induced dimerization of the fusion protein in CHO cells.

Mots-clés Agrovoc : biologie moléculaire, chimère, péroxydase, immunoglobuline, antimicrobien, macrophage

Classification Agris : F30 - Génétique et amélioration des plantes
F60 - Physiologie et biochimie végétale

Auteurs et affiliations

• Tournay C.
• Courtoy P.J.
• Marodi L.
• Totté Philippe, CIRAD-EMVT-ELEVAGE-AGRICULTURE (KEN)
• Wérenne John
• Jacquet A.
• Garcia Quintana L.
• Bollen A.
• Moguilevsky N.

Source : Cirad - Agritrop (https://agritrop.cirad.fr/389724/)

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