title: Extracellular methemoglobin primes red blood cell aggregation in malaria: an in vitro mechanistic study.
abstract: Toxic byproducts from infected RBC cause rheological alteration and RBC aggregation. Malaria culture supernatant has the ability to exhibit RBC aggregation. Ammonium sulfate fractionation and immunodepletion of methemoglobin from culture supernatant confirms methemoglobin as a major aggregant. In vitro treatment of RBC with methemoglobin induces irreversible high order RBC aggregates, resistant to shear stress and physical forces. Methemoglobin-mediated ROS generation in the external micro-environment to develop oxidative stress close to RBC membrane seems to be responsible for initiating and forming high order RBC aggregates through phosphatidyl-serine externalization. Removal of oxidative stress through antioxidant treatment abolishes high order RBC aggregate formation. In conclusion, we discovered a novel pathway of methemoglobin-mediated RBC aggregation and its potential role in patho-physiological effects during malaria.
authors: Malaria Research Group, Department of Biotechnology, Indian Institute of Technology-Guwahati, Guwahati 781039, Assam, India.
authors: S N
authors: SN
authors: Balaji
authors: Vishal
authors: V
authors: Trivedi
mesh_terms: D000328:Adult; D000740:Anemia / Q000209:etiology / Q000517:prevention & control; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use; D001692:Biological Transport / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000378:metabolism; D004903:Erythrocyte Aggregation / Q000187:drug effects; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism / Q000469:parasitology; D005260:Female; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000378:metabolism* / Q000469:parasitology / Q000503:physiopathology; D008297:Male; D008706:Methemoglobin / Q000378:metabolism*; D058990:Molecular Targeted Therapy; D018384:Oxidative Stress / Q000187:drug effects; D010718:Phosphatidylserines / Q000378:metabolism; D010963:Plasmodium falciparum / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013499:Surface Properties / Q000187:drug effects; D014652:Vascular Diseases / Q000209:etiology / Q000517:prevention & control; D055815:Young Adult
chemical_list: D000975:Antioxidants; D017077:Culture Media, Conditioned; D010718:Phosphatidylserines; D017382:Reactive Oxygen Species; D008706:Methemoglobin