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Sickle mouse red cells activate endothelium by heme‐mediated peroxide generation and promote red cell and leukocyte adhesion
Author(s) -
Kaul Dhananjay K.,
Shah Janki,
Suzuka Sandra,
Fabry Mary E.
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1137.8
Subject(s) - endothelium , chemistry , intravital microscopy , red blood cell , autoxidation , adhesion , microcirculation , peroxide , microbiology and biotechnology , reactive oxygen species , cell adhesion , hemoglobin , superoxide dismutase , heme , catalase , biochemistry , biology , cell , oxidative stress , medicine , endocrinology , organic chemistry , enzyme
Sickle red blood cells (SS RBCs) are known to generate reactive oxygen species due to autoxidation of hemoglobin S (HbS). We hypothesize that HbS autoxidation and peroxide generation in SS mouse RBCs will result in activation of quiescent endothelium. We, therefore, infused BERK SS RBCs into congenic C57BL mice. BERK mice RBCs express exclusively HbS. A bolus of 150 μl of FITC‐labeled or unlabeled RBCs (Hct 30%) was infused iv into C57BL mice, and intravital observations made in the cremaster microcirculation. Infusion of FITC‐labeled C57BL RBCs into C57BL mice resulted in rare or no RBC adhesion, suggesting no endothelial activation. In contrast, infusion of BERK RBCs into C57BL mice caused marked increase in adhesion of infused RBCs in venules, accompanied by leukocyte recruitment. When the cremaster preparation was suffused with dihydrorhodamine (DHR), an H 2 O 2 ‐sensitive probe, infusion of BERK RBCs, but not C57BL RBCs, resulted in increased endothelial fluorescence intensity. Infusion of BERK RBCs treated with catalase (100 U) to quench RBC‐generated peroxide inhibited DHR fluorescence, and adhesion of RBCs and leukocyte. Superoxide dismutase was relatively ineffective. These results suggest an obligatory role of heme‐mediated peroxide generation by SS RBC in endothelial activation, SS RBC adhesion and inflammatory effects in sickle cell disease. Supported by grants from American Heart Association and NIH (HL070047).