PMID- 10625210
OWN - NLM
STAT- MEDLINE
DCOM- 20000209
LR  - 20061115
IS  - 0094-6176 (Print)
IS  - 0094-6176 (Linking)
VI  - 25
IP  - 5
DP  - 1999
TI  - The putative mechanism of thrombosis in antiphospholipid syndrome: impairment of 
      the protein C and the fibrinolytic systems by monoclonal anticardiolipin 
      antibodies.
PG  - 503-7
AB  - The mechanism of thrombosis in patients with antiphospholipid syndrome is not 
      clear. To investigate it, we examined the effect of monoclonal anticardiolipin 
      (aCL) antibodies and beta2-glycoprotein I (beta2-GPI), which is required for 
      formation of the aCL epitopes, on activated protein C (APC) and on fibrinolytic 
      activity. First, APC activities were measured in the presence and absence of 
      beta2-GPI or gamma M immunoglobulin (IgM) monoclonal aCLs (EY1C8 and EY2C9), or 
      both, established from peripheral blood lymphocytes obtained from a patient with 
      aCL. beta2-GPI exhibited a procoagulant activity by inhibiting APC activity as 
      well as an anticoagulant activity by inhibiting thrombin generation. Any further 
      inhibition of APC activity was caused by monoclonal aCL, and then only in the 
      presence of beta2-GPI. The remaining tissue plasminogen activator (t-PA) of the 
      sample consisting of beta2-GPI, two-chain recombinant t-PA, and plasminogen 
      activator inhibitor (PAI)-1 was measured by a chromogenic assay using the 
      synthetic substrate S-2251, Glu-plasminogen, and soluble fibrin monomer. 
      beta2-GPI protected t-PA activity from inhibition by PAI-1. However, monoclonal 
      aCLs (EY1C8 and EY2C9) inhibited the effect of beta2-GPI on fibrinolytic 
      activity; that is, monoclonal aCLs inhibited fibrinolytic activity by elevating 
      PAI-1 activity. Thrombosis in patients with aCL can be explained in part by both 
      the inhibition of APC anticoagulant activity and the impairment of fibrinolytic 
      activity by aCL.
FAU - Ieko, M
AU  - Ieko M
AD  - Department of Internal Medicine, School of Dentistry, Health Sciences University 
      of Hokkaido, Ishikari-Toubetsu, Japan.
FAU - Sawada, K I
AU  - Sawada KI
FAU - Koike, T
AU  - Koike T
FAU - Notoya, A
AU  - Notoya A
FAU - Mukai, M
AU  - Mukai M
FAU - Kohno, M
AU  - Kohno M
FAU - Wada, N
AU  - Wada N
FAU - Itoh, T
AU  - Itoh T
FAU - Yoshioka, N
AU  - Yoshioka N
LA  - eng
PT  - Journal Article
PT  - Review
PL  - United States
TA  - Semin Thromb Hemost
JT  - Seminars in thrombosis and hemostasis
JID - 0431155
RN  - 0 (Antibodies, Anticardiolipin)
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Anticoagulants)
RN  - 0 (Glycoproteins)
RN  - 0 (Protein C)
RN  - 0 (beta 2-Glycoprotein I)
SB  - IM
MH  - Antibodies, Anticardiolipin/pharmacology
MH  - Antibodies, Monoclonal/pharmacology
MH  - Anticoagulants/pharmacology
MH  - Antiphospholipid Syndrome/*complications/metabolism
MH  - Fibrinolysis/drug effects
MH  - Glycoproteins/pharmacology
MH  - Humans
MH  - Protein C/drug effects
MH  - Thrombosis/*etiology/*metabolism
MH  - beta 2-Glycoprotein I
RF  - 20
EDAT- 2000/01/07 00:00
MHDA- 2000/01/07 00:01
CRDT- 2000/01/07 00:00
PHST- 2000/01/07 00:00 [pubmed]
PHST- 2000/01/07 00:01 [medline]
PHST- 2000/01/07 00:00 [entrez]
AID - 10.1055/s-2007-994958 [doi]
PST - ppublish
SO  - Semin Thromb Hemost. 1999;25(5):503-7. doi: 10.1055/s-2007-994958.