Anti-P-selectin antibody decreases inflammation and thrombus formation in venous thrombosis.
OBJECTIVE
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.
Downing
L J
LJ
Department of Surgery, University of Michigan Medical Center, Ann Arbor 48109-0329, USA.
Wakefield
T W
TW
Strieter
R M
RM
Prince
M R
MR
Londy
F J
FJ
Fowlkes
J B
JB
Hulin
M S
MS
Kadell
A M
AM
Wilke
C A
CA
Brown
S L
SL
Wrobleski
S K
SK
Burdick
M D
MD
Anderson
D C
DC
Greenfield
L J
LJ
D000208:Acute Disease; D000818:Animals; D000906:Antibodies / Q000097:blood; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D002908:Chronic Disease; D003287:Contrast Media; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D005682:Gadolinium; D007084:Iliac Vein / Q000000981:diagnostic imaging / Q000473:pathology; D018810:Magnetic Resonance Angiography; D019007:P-Selectin / Q000276:immunology*; D010215:Papio; D011859:Radiography; D013927:Thrombosis / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D013997:Time Factors; D014463:Ultrasonography; D014657:Vasculitis / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D014682:Vena Cava, Inferior / Q000000981:diagnostic imaging / Q000473:pathology
D000906:Antibodies; D000911:Antibodies, Monoclonal; C105956:CY1748 monoclonal antibody; D003287:Contrast Media; C105957:GA6 monoclonal antibody; D019007:P-Selectin; D005682:Gadolinium