Document Detail


Anti-P-selectin antibody decreases inflammation and thrombus formation in venous thrombosis.
MedLine Citation:
PMID:  9152309     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: Venous thrombosis and inflammation are interrelated. P-selectin contributes to activation of leukocyte-mediated inflammation. Therefore, we hypothesized that the neutralization of P-selectin would decrease vein wall inflammation and thrombosis.
METHODS: Twelve baboons underwent infrarenal inferior vena caval balloon occlusion to induce thrombosis. Two groups of four baboons received neutralizing intravenous anti-P-selectin antibody (PSab) GA6 or CY1748 before occlusion and at days 2 and 4. Four baboons received saline control injections. One baboon per group was killed at days 2, 6, and 13, and at 2 months. Analysis included phlebography, ultrasound, gadolinium (Gd)-enhanced magnetic resonance venography (reflecting vein wall inflammation), and histologic, morphometric, and protein evaluation of the vein wall. Thrombus presence or absence was assessed.
RESULTS: By day 2 in PSab baboons, vein wall Gd enhancement was decreased in the mid-inferior vena cava and the right iliac vein (p < 0.05; GA6 vs control baboons), normalizing by 2 months. The mid-inferior vena cava revealed fewer neutrophils and total leukocytes in PSab baboons; however, for GA6 in the right iliac vein these decreases were not present despite the absence of Gd enhancement; they were decreased with CY1748. PSab baboons demonstrated significantly less thrombus than control baboons (p < 0.01, GA6 and CY1748 vs control baboons).
CONCLUSIONS: Anti-P-selectin antibody decreases vein wall inflammation and thrombus formation. Inhibition of P-selectin may be useful in venous thrombosis prophylaxis.
Authors:
L J Downing; T W Wakefield; R M Strieter; M R Prince; F J Londy; J B Fowlkes; M S Hulin; A M Kadell; C A Wilke; S L Brown; S K Wrobleski; M D Burdick; D C Anderson; L J Greenfield
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of vascular surgery : official publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter     Volume:  25     ISSN:  0741-5214     ISO Abbreviation:  J. Vasc. Surg.     Publication Date:  1997 May 
Date Detail:
Created Date:  1997-06-06     Completed Date:  1997-06-06     Revised Date:  2011-07-29    
Medline Journal Info:
Nlm Unique ID:  8407742     Medline TA:  J Vasc Surg     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  816-27; discussion 828     Citation Subset:  IM    
Affiliation:
Department of Surgery, University of Michigan Medical Center, Ann Arbor 48109-0329, USA.
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MeSH Terms
Descriptor/Qualifier:
Acute Disease
Animals
Antibodies / blood
Antibodies, Monoclonal / therapeutic use*
Chronic Disease
Contrast Media
Disease Models, Animal
Drug Evaluation, Preclinical
Gadolinium / diagnostic use
Iliac Vein* / pathology,  radiography,  ultrasonography
Magnetic Resonance Angiography
P-Selectin / immunology*
Papio
Thrombosis / diagnosis,  drug therapy*,  immunology,  pathology
Time Factors
Vasculitis / diagnosis,  drug therapy*,  immunology,  pathology
Vena Cava, Inferior* / pathology,  radiography,  ultrasonography
Grant Support
ID/Acronym/Agency:
HL50057/HL/NHLBI NIH HHS; HL53355/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Antibodies; 0/Antibodies, Monoclonal; 0/CY1748 monoclonal antibody; 0/Contrast Media; 0/GA6 monoclonal antibody; 0/P-Selectin; 7440-54-2/Gadolinium

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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