Mercury leads to abnormal red blood cell adhesion to laminin mediated by membrane sulfatides

Birnur Akkaya; Erdem Kucukal; Jane A Little; Umut A Gurkan

doi:10.1016/j.bbamem.2019.03.008

Mercury leads to abnormal red blood cell adhesion to laminin mediated by membrane sulfatides

Biochim Biophys Acta Biomembr. 2019 Jun 1;1861(6):1162-1171. doi: 10.1016/j.bbamem.2019.03.008. Epub 2019 Mar 16.

Authors

Birnur Akkaya¹, Erdem Kucukal², Jane A Little³, Umut A Gurkan⁴

Affiliations

¹ Science Faculty, Department of Molecular Biology and Genetics Department, Cumhuriyet University, Sivas, Turkey; Case Biomanufacturing and Microfabrication Laboratory, Mechanical and Aerospace Engineering Department, Case Western Reserve University, Cleveland, OH, USA.
² Case Biomanufacturing and Microfabrication Laboratory, Mechanical and Aerospace Engineering Department, Case Western Reserve University, Cleveland, OH, USA.
³ Department of Hematology and Oncology, School of Medicine, Case Western Reserve University, Cleveland, OH, USA; University Hospitals Cleveland Medical Center, Cleveland, OH, USA.
⁴ Case Biomanufacturing and Microfabrication Laboratory, Mechanical and Aerospace Engineering Department, Case Western Reserve University, Cleveland, OH, USA; Biomedical Engineering Department, Case Western Reserve University, Cleveland, OH, USA; Department of Orthopaedics, Case Western Reserve University, Cleveland, OH, USA. Electronic address: umut@case.edu.

Abstract

Exposure to mercury is associated with numerous health problems, affecting different parts of the human body, including the nervous and cardiovascular systems in adults and children; however, the underlying mechanisms are yet to be fully elucidated. We investigated the role of membrane sulfatide on mercuric ion (Hg²⁺) mediated red blood cell (RBC) adhesion to a sub-endothelial matrix protein, laminin, using a microfluidic system that mimics microphysiological flow conditions. We exposed whole blood to mercury (HgCl₂), at a range of concentrations to mimic acute (high dose) and chronic (low dose) exposure, and examined RBC adhesion to immobilized laminin in microchannels at physiological flow conditions. Exposure of RBCs to both acute and chronic levels of Hg²⁺ resulted in elevated adhesive interactions between RBCs and laminin depending on the concentration of HgCl₂ and exposure duration. BCAM-Lu chimer significantly inhibited the adhesion of RBCs that had been treated with 50 μM of HgCl₂ solution for 1 h at 37 °C, while it did not prevent the adhesion of 3 h and 24 h Hg²⁺-treated RBCs. Sulfatide significantly inhibited the adhesion of RBC that had been treated with 50 μM of HgCl₂ solution for 1 h at 37 °C and 0.5 μM of HgCl₂ solution for 24 h at room temperature (RT). We demonstrated that RBC BCAM-Lu and RBC sulfatides bind to immobilized laminin, following exposure of RBCs to mercuric ions. The results of this study are significant considering the potential associations between sulfatides, red blood cells, mercury exposure, and cardiovascular diseases.

Keywords: Adhesion to laminin; Erythrocyte; Mercury; Mercury exposure; Red blood cell; Sulfatides.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Cell Adhesion / drug effects*
Dose-Response Relationship, Drug
Erythrocytes, Abnormal / cytology
Erythrocytes, Abnormal / metabolism*
Humans
Laminin / metabolism
Mercuric Chloride / administration & dosage
Mercuric Chloride / toxicity*

Substances

Laminin
Mercuric Chloride

Grants and funding

R01 HL133574/HL/NHLBI NIH HHS/United States