Inflammatory and oxidative stress phenotypes in transgenic sickle cell mice.
The Townes mouse model of homozygous sickle cell disease (SS) has emerged as the major experimental model for studying pathophysiological mechanisms of human sickle cell disease (SCD). We therefore investigated hematological and hemorheological parameters as well as organ-specific inflammatory and oxidative stress molecular profiles in these animals in steady state conditions. Evidences of SCD-related intravascular hemolysis, impaired red blood cell (RBC) deformability, leukocytosis and altered plasma nitric oxide byproducts (NOx) level were found in the SS mice. The SS mice have damaged, enlarged and dysfunctional spleen as attested by high AOPP levels, low SOD and GPx activities and low pro-inflammatory cytokines mRNA expression. SS mice exhibited cardiomegaly, high cardiac mRNA levels of proinflammatory markers and low cardiac GPx activity. While lungs did not display any noticeable defects, liver and kidney were particularly sensitive to oxidative stress and inflammation as suggested by high AOPP levels in both organs, elevated renal NF-κB and TNF-α, and increased hepatic VCAM-1 and IL-1β. Our data indicate a tissue-specific phenotype regarding oxidative stress and inflammation in SS mice that may help to optimize the development of novel potential drug treatments.
Inter-university Laboratory of Human Movement Science EA7424, Vascular biology and Red Blood Cell Team, University Claude Bernard Lyon 1, University of Lyon, Villeurbanne, France; Laboratory of Excellence "GR-Ex", Paris, France.
Emmanuelle
E
Charrin
Division of Hematology/Oncology, Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA; Center for Translational and International Hematology, Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA 15261, USA.
Solomon Fiifi
SF
Ofori-Acquah
Inter-university Laboratory of Human Movement Science EA7424, Vascular biology and Red Blood Cell Team, University Claude Bernard Lyon 1, University of Lyon, Villeurbanne, France; Laboratory of Excellence "GR-Ex", Paris, France.
Elie
E
Nader
Inter-university Laboratory of Human Movement Science EA7424, Vascular biology and Red Blood Cell Team, University Claude Bernard Lyon 1, University of Lyon, Villeurbanne, France; Laboratory of Excellence "GR-Ex", Paris, France.
Sarah
S
Skinner
Inter-university Laboratory of Human Movement Science EA7424, Vascular biology and Red Blood Cell Team, University Claude Bernard Lyon 1, University of Lyon, Villeurbanne, France; Laboratory of Excellence "GR-Ex", Paris, France; Institut Universitaire de France, Paris, France.
Philippe
P
Connes
Inter-university Laboratory of Human Movement Science EA7424, Vascular biology and Red Blood Cell Team, University Claude Bernard Lyon 1, University of Lyon, Villeurbanne, France; Laboratory of Excellence "GR-Ex", Paris, France; Institut Universitaire de France, Paris, France.
Vincent
V
Pialoux
Inter-university Laboratory of Human Movement Science EA7424, Vascular biology and Red Blood Cell Team, University Claude Bernard Lyon 1, University of Lyon, Villeurbanne, France; Laboratory of Excellence "GR-Ex", Paris, France; Laboratory of Biochemistry and Molecular Biology, Hospital Edouard Herriot, Lyon, France.
Philippe
P
Joly
Inter-university Laboratory of Human Movement Science EA7424, Vascular biology and Red Blood Cell Team, University Claude Bernard Lyon 1, University of Lyon, Villeurbanne, France; Laboratory of Excellence "GR-Ex", Paris, France. Electronic address: cyril.martin@univ-lyon1.fr.
Cyril
C
Martin
D000755:Anemia, Sickle Cell / Q000150:complications / Q000378:metabolism* / Q000473:pathology*; D000818:Animals; D006332:Cardiomegaly / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D006402:Hematologic Diseases; D018056:Hemorheology; D007249:Inflammation; D007674:Kidney Diseases / Q000378:metabolism / Q000473:pathology; D008107:Liver Diseases / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D009928:Organ Specificity; D018384:Oxidative Stress; D010641:Phenotype; D013158:Splenic Diseases / Q000378:metabolism / Q000473:pathology
Inflammation; Nitric oxide; Oxidative stress; Sickle cell disease