Increased expression of phospholipid scramblase 1 in monocytes from patients with systemic lupus erythematosus.
OBJECTIVE
A high incidence of thromboembolic events has been reported in patients with systemic lupus erythematosus (SLE). Phosphatidylserine (PS) is normally sequestered in the inner leaflet of cell membranes. Externalization of PS during cell activation is mediated by phospholipid scramblase 1 (PLSCR1) and has a central role in promoting blood coagulation. We investigated the underlying pathogenic status of thrombophilia in SLE by analyzing PLSCR1 expression on monocytes from patients with SLE.


METHODS
Sixty patients with SLE were evaluated. Twenty-three patients had antiphospholipid syndrome (APS/SLE). Plasma D-dimer levels were measured as a marker of fibrin turnover. The cDNA encoding human PLSCR1 was cloned from the total RNA extract from monocytes, and independent clones were sequenced. PLSCR1 mRNA expression in CD14+ cells was determined by real-time polymerase chain reaction. PS exposure on CD14+ cell surface was analyzed by flow cytometry.


RESULTS
Elevated D-dimer levels were found in plasma from SLE patients. Three splice variants of PLSCR1 mRNA were identified in all subjects, and levels of full-length PLSCR1 mRNA were significantly increased in SLE compared to healthy controls (2.9 +/- 1.5 vs 1.3 +/- 0.4, respectively; p < 0.0001). Flow-cytometry analysis showed relative enhancement of PS exposure in the surface of CD14+ cells in SLE patients compared to healthy controls.


CONCLUSIONS
Novel PLSCR1 splice variants were identified. Monocytes in SLE patients had enhanced PLSCR1 mRNA expression, as well as increased fibrin turnover and cell-surface PS exposure, indicating that PLSCR1 may, in part, contribute to the prothrombotic tendency in SLE.
Suzuki
Eriko
E
Department of Medicine II, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
Amengual
Olga
O
Atsumi
Tatsuya
T
Oku
Kenji
K
Hashimoto
Toko
T
Kataoka
Hiroshi
H
Horita
Tetsuya
T
Yasuda
Shinsuke
S
Ieko
Masahiro
M
Fukushima
Kazuaki
K
Koike
Takao
T
D000328:Adult; D000368:Aged; D016736:Antiphospholipid Syndrome / Q000097:blood / Q000201:enzymology; D002462:Cell Membrane / Q000378:metabolism; D005089:Exocytosis / Q000502:physiology*; D005260:Female; D005337:Fibrin / Q000378:metabolism; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D005434:Flow Cytometry; D015870:Gene Expression; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000201:enzymology* / Q000473:pathology; D010718:Phosphatidylserines / Q000378:metabolism; D049294:Phospholipid Transfer Proteins / Q000235:genetics / Q000378:metabolism*; D020033:Protein Isoforms; D012326:RNA Splicing; D012333:RNA, Messenger / Q000378:metabolism; D055815:Young Adult
D005338:Fibrin Fibrinogen Degradation Products; C493422:PLSCR1 protein, human; D010718:Phosphatidylserines; D049294:Phospholipid Transfer Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; C036309:fibrin fragment D; D005337:Fibrin