Anti-P-selectin antibody decreases inflammation and thrombus formation in venous thrombosis.

Abstract

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
• Journal: Journal of vascular surgery (J Vasc Surg) Vol. 25 Issue 5 Pg. 816-27; discussion 828 (May 1997) ISSN: 0741-5214 [Print] United States
• PMID: 9152309 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antibodies
• Antibodies, Monoclonal
• CY1748 monoclonal antibody
• Contrast Media
• GA6 monoclonal antibody
• P-Selectin
• Gadolinium

Topics

• Acute Disease
• Animals
• Antibodies (blood)
• Antibodies, Monoclonal (therapeutic use)
• Chronic Disease
• Contrast Media
• Disease Models, Animal
• Drug Evaluation, Preclinical
• Gadolinium
• Iliac Vein (diagnostic imaging, pathology)
• Magnetic Resonance Angiography
• P-Selectin (immunology)
• Papio
• Radiography
• Thrombosis (diagnosis, drug therapy, immunology, pathology)
• Time Factors
• Ultrasonography
• Vasculitis (diagnosis, drug therapy, immunology, pathology)
• Vena Cava, Inferior (diagnostic imaging, pathology)