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Cerebrovascular Endothelial Cell Activation in Paediatric Diabetic Ketoacidosis
Author(s) -
Omatsu Tatsushi,
Cepinskas Gediminas,
Fraser Douglas D
Publication year - 2013
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.27.1_supplement.870.8
Subject(s) - medicine , diabetic ketoacidosis , endothelial activation , diabetes mellitus , inflammation , endocrinology , sepsis , type 1 diabetes , endothelial dysfunction , endothelial stem cell , immunology , in vitro , biology , biochemistry
Diabetic ketoacidosis (DKA) in children is associated with intracranial vascular complications. The mechanisms of DKA‐induced vascular dysfunction are unclear. We aimed to assess the effects/mechanisms of DKA plasma on activation of human cerebrovascular endothelial cells (hCMEC/D3; provided by Dr. P.O. Couraud, INSERM). Methods DKA‐blood plasma was obtained from paediatric patients with either DKA or well‐controlled type‐1 diabetes (control; CON). The levels of 21 inflammation‐relevant analytes in blood were assessed. In vitro hCMEC/D3 were stimulated with 20% (v/v) CON‐ or DKA‐plasma and assessed for activation markers. Results DKA in children resulted in increased circulating levels of IL‐2, IL‐6, IL‐8, GRO, INFα2, and G‐CSF. Stimulation of hCMEC/D3 with DKA‐plasma induced production of ROS and increased PMN‐leukocyte adhesion to hCMEC/D3 under “flow” conditions (shear stress 0.35 dyn/cm 2 ). PMN adhesion was replicated by stimulating hCMEC/D3 with IL‐8 and/or GROα (at the levels detected in DKA‐plasma), the phenomenon that was suppressed by neutralizing anti‐CXCR1 and/or CXCR2 antibodies. Conclusions DKA elicits systemic inflammation associated with increased oxidative stress and up‐regulation of the pro‐adhesive phenotype in cerebrovascular endothelium, potentially contributing to DKA‐associated intracranial vascular complications.