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

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, T. B. Baxter

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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.

Original languageEnglish (US)
Pages (from-to)816-828
Number of pages13
JournalJournal of vascular surgery
Volume25
Issue number5
DOIs
StatePublished - Jan 1 1997

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P-Selectin
Papio
Venous Thrombosis
Thrombosis
Inflammation
Antibodies
Veins
Gadolinium
Iliac Vein
Phlebography
Inferior Vena Cava
Leukocytes
Balloon Occlusion
Venae Cavae
Neutrophils
Magnetic Resonance Spectroscopy
Injections

ASJC Scopus subject areas

  • Surgery
  • Cardiology and Cardiovascular Medicine

Cite this

Downing, L. J., Wakefield, T. W., Strieter, R. M., Prince, M. R., Londy, F. J., Fowlkes, J. B., ... Baxter, T. B. (1997). Anti-P-selectin antibody decreases inflammation and thrombus formation in venous thrombosis. Journal of vascular surgery, 25(5), 816-828. https://doi.org/10.1016/S0741-5214(97)70211-8

Anti-P-selectin antibody decreases inflammation and thrombus formation in venous thrombosis. / Downing, L. J.; Wakefield, T. W.; Strieter, R. M.; Prince, M. R.; Londy, F. J.; Fowlkes, J. B.; Hulin, M. S.; Kadell, A. M.; Wilke, C. A.; Brown, S. L.; Wrobleski, S. K.; Burdick, M. D.; Anderson, D. C.; Greenfield, L. J.; Baxter, T. B.

In: Journal of vascular surgery, Vol. 25, No. 5, 01.01.1997, p. 816-828.

Research output: Contribution to journalArticle

Downing, LJ, Wakefield, TW, Strieter, RM, Prince, MR, Londy, FJ, Fowlkes, JB, Hulin, MS, Kadell, AM, Wilke, CA, Brown, SL, Wrobleski, SK, Burdick, MD, Anderson, DC, Greenfield, LJ & Baxter, TB 1997, 'Anti-P-selectin antibody decreases inflammation and thrombus formation in venous thrombosis', Journal of vascular surgery, vol. 25, no. 5, pp. 816-828. https://doi.org/10.1016/S0741-5214(97)70211-8
Downing, L. J. ; Wakefield, T. W. ; Strieter, R. M. ; Prince, M. R. ; Londy, F. J. ; Fowlkes, J. B. ; Hulin, M. S. ; Kadell, A. M. ; Wilke, C. A. ; Brown, S. L. ; Wrobleski, S. K. ; Burdick, M. D. ; Anderson, D. C. ; Greenfield, L. J. ; Baxter, T. B. / Anti-P-selectin antibody decreases inflammation and thrombus formation in venous thrombosis. In: Journal of vascular surgery. 1997 ; Vol. 25, No. 5. pp. 816-828.
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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.",
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T1 - Anti-P-selectin antibody decreases inflammation and thrombus formation in venous thrombosis

AU - Downing, L. J.

AU - Wakefield, T. W.

AU - Strieter, R. M.

AU - Prince, M. R.

AU - Londy, F. J.

AU - Fowlkes, J. B.

AU - Hulin, M. S.

AU - Kadell, A. M.

AU - Wilke, C. A.

AU - Brown, S. L.

AU - Wrobleski, S. K.

AU - Burdick, M. D.

AU - Anderson, D. C.

AU - Greenfield, L. J.

AU - Baxter, T. B.

PY - 1997/1/1

Y1 - 1997/1/1

N2 - 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.

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