title: Interaction of recombinant octameric hemoglobin with endothelial cells.
abstract: Hemoglobin-based oxygen carriers (HBOCs) may generate oxidative stress, vasoconstriction and inflammation. To reduce these undesirable vasoactive properties, we increased hemoglobin (Hb) molecular size by genetic engineering with octameric Hb, recombinant (r) HbβG83C. We investigate the potential side effects of rHbβG83C on endothelial cells. The rHbβG83C has no impact on cell viability, and induces a huge repression of endothelial nitric oxide synthase gene transcription, a marker of vasomotion. No induction of Intermolecular-Adhesion Molecule 1 and E-selectin (inflammatory markers) transcription was seen. In the presence of rHbβG83C, the transcription of heme oxygenase-1 (oxidative stress marker) is weakly increased compared to the two other HBOCs (references) or Voluven (control). This genetically engineered octameric Hb, based on a human Hb βG83C mutant, leads to little impact at the level of endothelial cell inflammatory response and thus appears as an interesting molecule for HBOC development.
authors.affiliation: Université de Lorraine, UMR CNRS 7561, Groupe Ingénierie Cellulaire et Tissulaire, Faculté de médecine, 5450 Vandoeuvre-lès-Nancy, France; Université de Lorraine, CITHEFOR EA 3452, Faculté de Pharmacie, BP 80403, 54001 Nancy Cedex, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Gaucher
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (Inserm) U779, Université Paris XI, 78, rue du Général-Leclerc, 94275 Le Kremlin-Bicêtre, France.
authors.forename: Élisa
authors.initials: É
authors.lastname: Domingues-Hamdi
authors.affiliation: Laboratoire d'immunologie, Faculté de Médecine - CHU Nancy, 54500 Vandoeuvre-lès-Nancy, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Prin-Mathieu
authors.affiliation: Université de Lorraine, UMR CNRS 7561, Groupe Ingénierie Cellulaire et Tissulaire, Faculté de médecine, 5450 Vandoeuvre-lès-Nancy, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Menu
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (Inserm) U779, Université Paris XI, 78, rue du Général-Leclerc, 94275 Le Kremlin-Bicêtre, France. Electronic address: veronique.baudin-creuza@inserm.fr.
authors.forename: Véronique
authors.initials: V
authors.lastname: Baudin-Creuza
mesh_terms: D015415:Biomarkers; D001802:Blood Substitutes / Q000494:pharmacology* / Q000633:toxicity; D002470:Cell Survival / Q000187:drug effects; D003911:Dextrans / Q000494:pharmacology / Q000633:toxicity; D015536:Down-Regulation / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D019040:E-Selectin / Q000096:biosynthesis / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000096:biosynthesis / Q000235:genetics; D006454:Hemoglobins / Q000032:analysis / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D006895:Hydroxyethyl Starch Derivatives / Q000494:pharmacology / Q000633:toxicity; D007249:Inflammation / Q000139:chemically induced; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis / Q000235:genetics; D008706:Methemoglobin / Q000032:analysis; D008958:Models, Molecular; D052250:Nitric Oxide Synthase Type III / Q000096:biosynthesis / Q000235:genetics; D018384:Oxidative Stress / Q000187:drug effects; D010952:Plasma Substitutes / Q000494:pharmacology / Q000633:toxicity; D011487:Protein Conformation; D060888:Real-Time Polymerase Chain Reaction; D014661:Vasoconstriction / Q000187:drug effects
chemical_list: D015415:Biomarkers; D001802:Blood Substitutes; D003911:Dextrans; D019040:E-Selectin; C485123:HES 130-0.4; D006454:Hemoglobins; D006895:Hydroxyethyl Starch Derivatives; D010952:Plasma Substitutes; C402601:hemoglobin glutamer-200; C095659:hemoglobin-dextran 10-benzene-tetracarboxylate; D018799:Intercellular Adhesion Molecule-1; D008706:Methemoglobin; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1
keywords: Adhesion molecules; Cellules endothéliales; Endothelial cell; Hemoglobin-based oxygen carriers; Hémoglobine recombinante; Molécules d’adhésion; Octamer; Octamère; Recombinant hemoglobin; Transporteur d’oxygène à base d’hémoglobine; Vasoactivity; Vasoactivité