Characterizations and proteome analysis of platelet-free plasma-derived microparticles in β-thalassemia/hemoglobin E patients.
Aggregatability and oxidative damage of red blood cells (RBCs), platelet activation and increased amount of blood cells-derived microparticles (MPs) are thought to be the etiologies for the thrombotic risk in thalassemia, but with unclear mechanisms. Here we report cellular origins and increases in number, oxidative stress status, and procoagulant activity, as well as altered proteome of MPs isolated from β-thal/HbE patients. Flow cytometric analysis revealed that β-thal/HbE patients had significantly higher levels of phosphatidylserine (PS)-bearing MPs in platelet-free plasma (PFP) as compared to normal subjects. The high levels of MPs correlated with not only the increased procoagulant activity but also the increased platelet counts. Additionally, these PS-bearing MPs were originated mostly from platelets and RBCs, both of which had increased levels of reactive oxygen species. Proteome analysis of MPs by 2-DE followed by Q-TOF MS and MS/MS analyses identified 29 proteins with significantly altered levels in MPs derived from β-thal/HbE patients (e.g. the increased levels of peroxiredoxin 6, apolipoprotein E, cyclophilin A and heat shock protein 90). These findings suggest that the oxidative damage in platelets and RBCs potentially induces production of MPs with altered proteome that may, in turn, facilitate thromboembolic complications, which are commonly found in thalassemic patients. This article is part of a Special Issue entitled: Integrated omics.
Department of Immunology and Office for Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
Porntip
P
Chaichompoo
Panida
P
Kumya
Ladawan
L
Khowawisetsut
Wararat
W
Chiangjong
Sakdithep
S
Chaiyarit
Nutkridta
N
Pongsakul
Noppadol
N
Sirithanaratanakul
Suthat
S
Fucharoen
Visith
V
Thongboonkerd
Kovit
K
Pattanapanyasat
D000328:Adult; D001798:Blood Proteins / Q000378:metabolism; D055252:Cell-Derived Microparticles / Q000378:metabolism*; D005260:Female; D006446:Hemoglobin E; D006456:Hemoglobinuria / Q000097:blood*; D006801:Humans; D008297:Male; D010949:Plasma / Q000378:metabolism*; D020543:Proteome / Q000378:metabolism*; D040901:Proteomics / Q000379:methods; D013923:Thromboembolism / Q000097:blood; D017086:beta-Thalassemia / Q000097:blood*
D001798:Blood Proteins; D020543:Proteome; D006446:Hemoglobin E