Human polymorphonuclear leukocytes produce and express functional tissue factor upon stimulation

Research output: Contribution to journalArticle

Abstract

Background: Blood-borne tissue factor (TF) plays a crucial role in thrombogenesis. Aim: To study whether polymorphonuclear leukocytes (PMN) are a source of TF. Methods and Results: Human PMN were carefully separated from ot her blood cells and stimulated for 3 min with purified P-selectin or the chemotactic peptide formyl-MetLeu- Phe (fMLP): they expressed both TF procoagulant activity, as identified by specific TF MoAb and inactivated factor VIIa blockade; and TF:Ag (four to six times), as shown by flowcytometry and immunocytochemistry. About 40% of permeabilized PMN, both resting and stimulated, contained TF:Ag, indicating that stimulation onlymodifies the location of TF:Ag within PMN. By real time-polymerase chain reaction (RT-PCR), a very low amount of TF mRNA was detectable in resting PMN, but a 3- to 5-fold increase was observed after 1-h stimulation with P-selectin or fMLP, respectively. Conclusions: These findings suggest that TF is not constitutively expressed in peripheral PMN, but can be up-regulated and produced upon stimulation and specific gene transcription, as for instance during contact with activated platelets or endothelium. The stored TF is rapidly expressed in vitro as a functional molecule on the surface of activated PMN. The availability of PMNTF supports the relevance of inflammatory cells and their interactionwith platelets for fibrin deposition and thrombus formation.

Original languageEnglish
Pages (from-to)1323-1330
Number of pages8
JournalJournal of Thrombosis and Haemostasis
Volume4
Issue number6
DOIs
Publication statusPublished - Jun 2006

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Thromboplastin
Neutrophils
P-Selectin
Blood Platelets
Factor VIIa
Fibrin
Endothelium
Real-Time Polymerase Chain Reaction
Blood Cells
Thrombosis
Immunohistochemistry
Messenger RNA
Peptides

Keywords

  • Inflammation
  • Platelet P-selectin
  • Polymorphonuclear leukocytes
  • Thrombosis
  • Tissue factor

ASJC Scopus subject areas

  • Medicine(all)

Cite this

@article{af6769c4e43b42649dc29cd94fee29ed,
title = "Human polymorphonuclear leukocytes produce and express functional tissue factor upon stimulation",
abstract = "Background: Blood-borne tissue factor (TF) plays a crucial role in thrombogenesis. Aim: To study whether polymorphonuclear leukocytes (PMN) are a source of TF. Methods and Results: Human PMN were carefully separated from ot her blood cells and stimulated for 3 min with purified P-selectin or the chemotactic peptide formyl-MetLeu- Phe (fMLP): they expressed both TF procoagulant activity, as identified by specific TF MoAb and inactivated factor VIIa blockade; and TF:Ag (four to six times), as shown by flowcytometry and immunocytochemistry. About 40{\%} of permeabilized PMN, both resting and stimulated, contained TF:Ag, indicating that stimulation onlymodifies the location of TF:Ag within PMN. By real time-polymerase chain reaction (RT-PCR), a very low amount of TF mRNA was detectable in resting PMN, but a 3- to 5-fold increase was observed after 1-h stimulation with P-selectin or fMLP, respectively. Conclusions: These findings suggest that TF is not constitutively expressed in peripheral PMN, but can be up-regulated and produced upon stimulation and specific gene transcription, as for instance during contact with activated platelets or endothelium. The stored TF is rapidly expressed in vitro as a functional molecule on the surface of activated PMN. The availability of PMNTF supports the relevance of inflammatory cells and their interactionwith platelets for fibrin deposition and thrombus formation.",
keywords = "Inflammation, Platelet P-selectin, Polymorphonuclear leukocytes, Thrombosis, Tissue factor",
author = "Norma Maugeri and M. Brambilla and M. Camera and A. Carbone and E. Tremoli and Donati, {M. B.} and {De Gaetano}, G. and C. Cerletti",
year = "2006",
month = "6",
doi = "10.1111/j.1538-7836.2006.01968.x",
language = "English",
volume = "4",
pages = "1323--1330",
journal = "Journal of Thrombosis and Haemostasis",
issn = "1538-7933",
publisher = "Wiley-Blackwell",
number = "6",

}

TY - JOUR

T1 - Human polymorphonuclear leukocytes produce and express functional tissue factor upon stimulation

AU - Maugeri, Norma

AU - Brambilla, M.

AU - Camera, M.

AU - Carbone, A.

AU - Tremoli, E.

AU - Donati, M. B.

AU - De Gaetano, G.

AU - Cerletti, C.

PY - 2006/6

Y1 - 2006/6

N2 - Background: Blood-borne tissue factor (TF) plays a crucial role in thrombogenesis. Aim: To study whether polymorphonuclear leukocytes (PMN) are a source of TF. Methods and Results: Human PMN were carefully separated from ot her blood cells and stimulated for 3 min with purified P-selectin or the chemotactic peptide formyl-MetLeu- Phe (fMLP): they expressed both TF procoagulant activity, as identified by specific TF MoAb and inactivated factor VIIa blockade; and TF:Ag (four to six times), as shown by flowcytometry and immunocytochemistry. About 40% of permeabilized PMN, both resting and stimulated, contained TF:Ag, indicating that stimulation onlymodifies the location of TF:Ag within PMN. By real time-polymerase chain reaction (RT-PCR), a very low amount of TF mRNA was detectable in resting PMN, but a 3- to 5-fold increase was observed after 1-h stimulation with P-selectin or fMLP, respectively. Conclusions: These findings suggest that TF is not constitutively expressed in peripheral PMN, but can be up-regulated and produced upon stimulation and specific gene transcription, as for instance during contact with activated platelets or endothelium. The stored TF is rapidly expressed in vitro as a functional molecule on the surface of activated PMN. The availability of PMNTF supports the relevance of inflammatory cells and their interactionwith platelets for fibrin deposition and thrombus formation.

AB - Background: Blood-borne tissue factor (TF) plays a crucial role in thrombogenesis. Aim: To study whether polymorphonuclear leukocytes (PMN) are a source of TF. Methods and Results: Human PMN were carefully separated from ot her blood cells and stimulated for 3 min with purified P-selectin or the chemotactic peptide formyl-MetLeu- Phe (fMLP): they expressed both TF procoagulant activity, as identified by specific TF MoAb and inactivated factor VIIa blockade; and TF:Ag (four to six times), as shown by flowcytometry and immunocytochemistry. About 40% of permeabilized PMN, both resting and stimulated, contained TF:Ag, indicating that stimulation onlymodifies the location of TF:Ag within PMN. By real time-polymerase chain reaction (RT-PCR), a very low amount of TF mRNA was detectable in resting PMN, but a 3- to 5-fold increase was observed after 1-h stimulation with P-selectin or fMLP, respectively. Conclusions: These findings suggest that TF is not constitutively expressed in peripheral PMN, but can be up-regulated and produced upon stimulation and specific gene transcription, as for instance during contact with activated platelets or endothelium. The stored TF is rapidly expressed in vitro as a functional molecule on the surface of activated PMN. The availability of PMNTF supports the relevance of inflammatory cells and their interactionwith platelets for fibrin deposition and thrombus formation.

KW - Inflammation

KW - Platelet P-selectin

KW - Polymorphonuclear leukocytes

KW - Thrombosis

KW - Tissue factor

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U2 - 10.1111/j.1538-7836.2006.01968.x

DO - 10.1111/j.1538-7836.2006.01968.x

M3 - Article

C2 - 16706978

AN - SCOPUS:33646820296

VL - 4

SP - 1323

EP - 1330

JO - Journal of Thrombosis and Haemostasis

JF - Journal of Thrombosis and Haemostasis

SN - 1538-7933

IS - 6

ER -