Antiadhesive effect of fibrinogen

A safeguard for thrombus stability

Valeryi K. Lishko, Timothy Burke, Tatiana Ugarova

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

The recruitment of phagocytic leukocytes to sites of vessel wall injury plays an important role in thrombus dissolution by proteases elaborated on their adhesion. However, leukocyte adhesion to the fibrin clot can be detrimental at the early stages of wound healing when hemostatic plug integrity is critical for preventing blood loss. Adhesion of circulating leukocytes to the insoluble fibrin(ogen) matrix is mediated by integrins and occurs in the presence of a high concentration of plasma fibrinogen. In this study, the possibility that soluble fibrinogen could protect fibrin from excessive adhesion of leukocytes was examined. Fibrinogen was a potent inhibitor of adhesion of U937 monocytoid cells and neutrophils to fibrin gel and immobilized fibrin(ogen). An investigation of the mechanism by which soluble fibrinogen exerts its influence on leukocyte adhesion indicated that it did not block integrins but rather associated with the fibrin(ogen) substrate. Consequently, leukocytes that engage fibrinogen molecules loosely bound to the surface of fibrin(ogen) matrix are not able to consolidate their grip on the substrate; subsequently, cells detach. This conclusion is based on the evidence obtained in adhesion studies using various cells and performed under static and flow conditions. These findings reveal a new role of fibrinogen in integrin-mediated leukocyte adhesion and suggest that this mechanism may protect the thrombus from premature dissolution.

Original languageEnglish (US)
Pages (from-to)1541-1549
Number of pages9
JournalBlood
Volume109
Issue number4
DOIs
StatePublished - Feb 15 2007

Fingerprint

Fibrin
Fibrinogen
Thrombosis
Leukocytes
Adhesion
Integrins
Dissolution
U937 Cells
Hand Strength
Hemostatics
Wound Healing
Substrates
Neutrophils
Peptide Hydrolases
Gels
Blood
estropipate
Plasmas
Wounds and Injuries
Molecules

ASJC Scopus subject areas

  • Hematology

Cite this

Antiadhesive effect of fibrinogen : A safeguard for thrombus stability. / Lishko, Valeryi K.; Burke, Timothy; Ugarova, Tatiana.

In: Blood, Vol. 109, No. 4, 15.02.2007, p. 1541-1549.

Research output: Contribution to journalArticle

Lishko, Valeryi K. ; Burke, Timothy ; Ugarova, Tatiana. / Antiadhesive effect of fibrinogen : A safeguard for thrombus stability. In: Blood. 2007 ; Vol. 109, No. 4. pp. 1541-1549.
@article{489bbe8914c54666b2d55b0b862fefca,
title = "Antiadhesive effect of fibrinogen: A safeguard for thrombus stability",
abstract = "The recruitment of phagocytic leukocytes to sites of vessel wall injury plays an important role in thrombus dissolution by proteases elaborated on their adhesion. However, leukocyte adhesion to the fibrin clot can be detrimental at the early stages of wound healing when hemostatic plug integrity is critical for preventing blood loss. Adhesion of circulating leukocytes to the insoluble fibrin(ogen) matrix is mediated by integrins and occurs in the presence of a high concentration of plasma fibrinogen. In this study, the possibility that soluble fibrinogen could protect fibrin from excessive adhesion of leukocytes was examined. Fibrinogen was a potent inhibitor of adhesion of U937 monocytoid cells and neutrophils to fibrin gel and immobilized fibrin(ogen). An investigation of the mechanism by which soluble fibrinogen exerts its influence on leukocyte adhesion indicated that it did not block integrins but rather associated with the fibrin(ogen) substrate. Consequently, leukocytes that engage fibrinogen molecules loosely bound to the surface of fibrin(ogen) matrix are not able to consolidate their grip on the substrate; subsequently, cells detach. This conclusion is based on the evidence obtained in adhesion studies using various cells and performed under static and flow conditions. These findings reveal a new role of fibrinogen in integrin-mediated leukocyte adhesion and suggest that this mechanism may protect the thrombus from premature dissolution.",
author = "Lishko, {Valeryi K.} and Timothy Burke and Tatiana Ugarova",
year = "2007",
month = "2",
day = "15",
doi = "10.1182/blood-2006-05-022764",
language = "English (US)",
volume = "109",
pages = "1541--1549",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "4",

}

TY - JOUR

T1 - Antiadhesive effect of fibrinogen

T2 - A safeguard for thrombus stability

AU - Lishko, Valeryi K.

AU - Burke, Timothy

AU - Ugarova, Tatiana

PY - 2007/2/15

Y1 - 2007/2/15

N2 - The recruitment of phagocytic leukocytes to sites of vessel wall injury plays an important role in thrombus dissolution by proteases elaborated on their adhesion. However, leukocyte adhesion to the fibrin clot can be detrimental at the early stages of wound healing when hemostatic plug integrity is critical for preventing blood loss. Adhesion of circulating leukocytes to the insoluble fibrin(ogen) matrix is mediated by integrins and occurs in the presence of a high concentration of plasma fibrinogen. In this study, the possibility that soluble fibrinogen could protect fibrin from excessive adhesion of leukocytes was examined. Fibrinogen was a potent inhibitor of adhesion of U937 monocytoid cells and neutrophils to fibrin gel and immobilized fibrin(ogen). An investigation of the mechanism by which soluble fibrinogen exerts its influence on leukocyte adhesion indicated that it did not block integrins but rather associated with the fibrin(ogen) substrate. Consequently, leukocytes that engage fibrinogen molecules loosely bound to the surface of fibrin(ogen) matrix are not able to consolidate their grip on the substrate; subsequently, cells detach. This conclusion is based on the evidence obtained in adhesion studies using various cells and performed under static and flow conditions. These findings reveal a new role of fibrinogen in integrin-mediated leukocyte adhesion and suggest that this mechanism may protect the thrombus from premature dissolution.

AB - The recruitment of phagocytic leukocytes to sites of vessel wall injury plays an important role in thrombus dissolution by proteases elaborated on their adhesion. However, leukocyte adhesion to the fibrin clot can be detrimental at the early stages of wound healing when hemostatic plug integrity is critical for preventing blood loss. Adhesion of circulating leukocytes to the insoluble fibrin(ogen) matrix is mediated by integrins and occurs in the presence of a high concentration of plasma fibrinogen. In this study, the possibility that soluble fibrinogen could protect fibrin from excessive adhesion of leukocytes was examined. Fibrinogen was a potent inhibitor of adhesion of U937 monocytoid cells and neutrophils to fibrin gel and immobilized fibrin(ogen). An investigation of the mechanism by which soluble fibrinogen exerts its influence on leukocyte adhesion indicated that it did not block integrins but rather associated with the fibrin(ogen) substrate. Consequently, leukocytes that engage fibrinogen molecules loosely bound to the surface of fibrin(ogen) matrix are not able to consolidate their grip on the substrate; subsequently, cells detach. This conclusion is based on the evidence obtained in adhesion studies using various cells and performed under static and flow conditions. These findings reveal a new role of fibrinogen in integrin-mediated leukocyte adhesion and suggest that this mechanism may protect the thrombus from premature dissolution.

UR - http://www.scopus.com/inward/record.url?scp=33846911014&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33846911014&partnerID=8YFLogxK

U2 - 10.1182/blood-2006-05-022764

DO - 10.1182/blood-2006-05-022764

M3 - Article

VL - 109

SP - 1541

EP - 1549

JO - Blood

JF - Blood

SN - 0006-4971

IS - 4

ER -