PMID- 12638903
OWN - NLM
STAT- MEDLINE
DCOM- 20030911
LR  - 20121115
IS  - 0171-2985 (Print)
IS  - 0171-2985 (Linking)
VI  - 207
IP  - 1
DP  - 2003
TI  - Inhibition of ras by farnesylthiosalicylate significantly reduces the levels of 
      autoantibodies in two animal models of the antiphospholipid syndrome.
PG  - 47-50
AB  - BACKGROUND: Stimulation and proliferation of lymphocytes require activation of 
      Ras. S-farnesylthiosalicylic acid (FTS) is a synthetic substance that detaches 
      Ras from the inner cell membrane and induces its rapid degradation. 
      Antiphospholipid antibodies (aPL) are a heterogeneous group of antibodies 
      detected in patients with antiphospholipid syndrome (APS), which is associated 
      with thrombosis, pregnancy losses, and thrombocytopenia. OBJECTIVE: To examine 
      the effect of FTS treatment on aPL levels in a genetic autoimmune model (the 
      MRL/lpr mice) and in an induced model of APS. METHODS: Female Balb/C mice 
      immunized once with beta2-glycoprotein I (beta2-GPI) in complete Freund's 
      adjuvant (CFA) and female MRL/lpr mice were treated intraperitoneally with either 
      FTS (5 mg/Kg/day) or saline 3-5 times a week. aPL and anti-beta2-GPI antibodies 
      were measured by ELISA. RESULTS: FTS treatment 3 times a week resulted in 
      significant decreases of aPL and anti-beta2-GPI antibodies in both animal models. 
      In contrast, more frequent treatment (5 times a week) had no significant effect 
      on autantibody levels in both animal models. We further compared 2 protocols in 
      the induced APS model, one for alternate day treatment and the other for daily 
      treatment on the first 3 days each week, and found a decrease in autoantibody 
      levels only in the alternate day protocol. CONCLUSIONS: Inhibition of Ras 
      activation by FTS is effective in decreasing autoantibody levels in models of 
      APS. The differential modulation of immune function by alternate day compared to 
      daily treatment may provide better understanding of the role of Ras activation in 
      this system.
FAU - Katzav, Aviva
AU  - Katzav A
AD  - Dept. of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv, 
      Israel.
FAU - Kloog, Yoel
AU  - Kloog Y
FAU - Korczyn, Amos D
AU  - Korczyn AD
FAU - Molina, Vered
AU  - Molina V
FAU - Blank, Miri
AU  - Blank M
FAU - Shoenfeld, Yehuda
AU  - Shoenfeld Y
FAU - Chapman, Joab
AU  - Chapman J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - Immunobiology
JT  - Immunobiology
JID - 8002742
RN  - 0 (Antibodies, Antiphospholipid)
RN  - 0 (Autoantibodies)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Glycoproteins)
RN  - 0 (Salicylates)
RN  - 0 (beta 2-Glycoprotein I)
RN  - 0 (farnesylthiosalicylic acid)
RN  - 4602-84-0 (Farnesol)
RN  - 9007-81-2 (Freund's Adjuvant)
RN  - EC 3.6.5.2 (ras Proteins)
SB  - IM
MH  - Animals
MH  - Antibodies, Antiphospholipid/blood/immunology
MH  - Antiphospholipid Syndrome/*blood/immunology
MH  - Autoantibodies/*blood
MH  - Disease Models, Animal
MH  - Enzyme Inhibitors/*pharmacology
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Farnesol/*analogs & derivatives/*pharmacology
MH  - Female
MH  - Freund's Adjuvant/pharmacology
MH  - Glycoproteins/immunology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred MRL lpr
MH  - Salicylates/*pharmacology
MH  - Time Factors
MH  - beta 2-Glycoprotein I
MH  - ras Proteins/*antagonists & inhibitors
EDAT- 2003/03/18 04:00
MHDA- 2003/09/13 05:00
CRDT- 2003/03/18 04:00
PHST- 2003/03/18 04:00 [pubmed]
PHST- 2003/09/13 05:00 [medline]
PHST- 2003/03/18 04:00 [entrez]
AID - S0171-2985(04)70163-1 [pii]
AID - 10.1078/0171-2985-00208 [doi]
PST - ppublish
SO  - Immunobiology. 2003;207(1):47-50. doi: 10.1078/0171-2985-00208.