P-selectin can promote thrombus propagation independently of both von Willebrand factor and thrombospondin-1 in mice

P Prakash; M K Nayak; A K Chauhan

doi:10.1111/jth.13586

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P-selectin can promote thrombus propagation independently of both von Willebrand factor and thrombospondin-1 in mice

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P-selectin can promote thrombus propagation independently of both von Willebrand factor and thrombospondin-1 in mice

P Prakash, M K Nayak and A K Chauhan

Journal of thrombosis and haemostasis, Vol.15(2), pp.388-394

02/2017

DOI: 10.1111/jth.13586

PMCID: PMC5305620

PMID: 27943541

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Abstract

Essentials The main receptor for platelet glycoprotein (GP) Ibα is von Willebrand factor (VWF). P-selectin and thrombospondin-1 (TSP1) have been suggested as counter receptors for GPIbα. In a laser injury model, P-selectin promotes thrombus propagation independently of VWF and TSP1. In a laser injury model, thrombus persists in interleukin-4 receptor α/GPIbα-transgenic mice. Background P-selectin and thrombospondin-1 (TSP1) have been suggested as counter ligands that may mediate GPIbα-dependent thrombus growth independently of von Willebrand factor (VWF) in vitro. However, residual thrombus formation still persists in Vwf Tsp1 mice, suggesting existence of other mechanisms that modulate thrombus propagation. Objective We determined whether P-selectin modulates thrombus propagation in injured arterioles independently of TSP1 and VWF. Methods CD-62P blocking antibody in Vwf Tsp1 mice was used to inhibit P-selectin. We determined thrombus growth kinetics in two models of thrombosis: FeCl injury-induced and laser injury-induced thrombosis. Results In a 10% FeCl injury-induced thrombosis model, the initial platelet adhesion, time to form first thrombus, and non-occlusive residual thrombus growth kinetics were comparable between P-selectin-blocking antibody-treated Vwf Tsp1 mice and control IgG-treated Vwf Tsp1 mice. On the other hand, in a laser injury-induced thrombosis model, residual thrombus growth kinetics were significantly decreased in P-selectin-blocking antibody-treated Vwf Tsp1 mice vs. control IgG-treated Vwf Tsp1 mice. Because P-selectin has been suggested as a counter ligand for platelet GPIbα, we determined the role of GPIbα in a laser injury-induced thrombosis model. Surprisingly, in a laser injury model, unlike in a FeCl injury model, thrombus formation was not completely inhibited in IL4Rα/GPIbα-tg mice. Residual thrombus growth kinetics were comparable between P-selectin-blocking antibody-treated IL4Rα/GPIbα-tg mice and control IgG-treated IL4Rα/GPIbα-tg mice. Comparison of slopes over time showed that residual thrombus growth kinetics were comparable in P-selectin-blocking antibody-treated Vwf Tsp1 and control IgG-treated IL4Rα/GPIbα-tg mice Conclusion In a laser injury-induced thrombosis model, P-selectin modulates thrombus propagation independently of VWF and TSP1.

P-Selectin - metabolism

Mice, Inbred C57BL

Ferric Compounds - chemistry

Chlorides - chemistry

Mice, Knockout

Platelet Adhesiveness - drug effects

Thrombosis - metabolism

Animals

Blood Platelets - metabolism

Lasers

Platelet Activation

Anticoagulants - pharmacology

Protein Binding

Mice

Thrombospondin 1 - metabolism

Disease Models, Animal

Immunoglobulin G - metabolism

von Willebrand Factor - metabolism

Details

Title: Subtitle: P-selectin can promote thrombus propagation independently of both von Willebrand factor and thrombospondin-1 in mice
Creators: P Prakash - Department of Internal Medicine, University of Iowa, Iowa City, IA, USA
M K Nayak - Department of Internal Medicine, University of Iowa, Iowa City, IA, USA
A K Chauhan - Department of Internal Medicine, University of Iowa, Iowa City, IA, USA
Resource Type: Journal article
Publication Details: Journal of thrombosis and haemostasis, Vol.15(2), pp.388-394
DOI: 10.1111/jth.13586
PMID: 27943541
PMCID: PMC5305620
ISSN: 1538-7933
eISSN: 1538-7836
Grant note: R01 HL118246 / NHLBI NIH HHS R01 HL118742 / NHLBI NIH HHS
Language: English
Date published: 02/2017
Academic Unit: Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
Record Identifier: 9984094338202771

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