Interaction between integrin α9β1 and Vascular Cell Adhesion Molecule-1 (VCAM-1) inhibits neutrophil apoptosis: cross-talk between integrin and cytokine signalling pathways

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@article{6cbabcd55a2f4f0fa417efa647d42863,
title = "Interaction between integrin α9β1 and Vascular Cell Adhesion Molecule-1 (VCAM-1) inhibits neutrophil apoptosis: cross-talk between integrin and cytokine signalling pathways",
abstract = "According to the prevailing paradigm, neutrophils are short-lived cells that undergo spontaneous apoptosis within 24 hours of their release from the bone marrow. However, neutrophil survival can be significantly prolonged within inflamed tissue by cytokines, inflammatory mediators, and hypoxia. During screening experiments aimed at identifying the effect of the adhesive microenvironment on neutrophil survival, we found that VCAM-1 (CD106) was able to delay both spontaneous and Fas-induced apoptosis. VCAM-1-mediated survival was as efficient as that induced by the cytokine IFN-beta and provided an additive, increased delay in apoptosis when given in combination with IFN-beta. VCAM-1 delivered its antiapoptotic effect through binding the integrin alpha9beta1. The alpha9beta1 signaling pathway shares significant features with the IFN-beta survival signaling pathway, requiring PI3 kinase, NF-kappaB activation, as well as de novo protein synthesis, but the kinetics of NF-kappaB activation by VCAM-1 were slower and more sustained compared with IFN-beta. This study demonstrates a novel functional role for alpha9beta1 in neutrophil biology and suggests that adhesive signaling pathways provide an important extrinsic checkpoint for the resolution of inflammatory responses in tissues.",
author = "Ewan Ross and Michael Douglas and See Wong and Emma Ross and Stephen Curnow and Gerard Nash and George Rainger and Dagmar Scheel-Toellner and Janet Lord and Michael Salmon and Christopher Buckley",
year = "2005",
month = oct,
day = "13",
doi = "10.1182/blood-2005-07-2692",
language = "English",
volume = "107",
pages = "1178--1183",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "3",

}

RIS

TY - JOUR

T1 - Interaction between integrin α9β1 and Vascular Cell Adhesion Molecule-1 (VCAM-1) inhibits neutrophil apoptosis: cross-talk between integrin and cytokine signalling pathways

AU - Ross, Ewan

AU - Douglas, Michael

AU - Wong, See

AU - Ross, Emma

AU - Curnow, Stephen

AU - Nash, Gerard

AU - Rainger, George

AU - Scheel-Toellner, Dagmar

AU - Lord, Janet

AU - Salmon, Michael

AU - Buckley, Christopher

PY - 2005/10/13

Y1 - 2005/10/13

N2 - According to the prevailing paradigm, neutrophils are short-lived cells that undergo spontaneous apoptosis within 24 hours of their release from the bone marrow. However, neutrophil survival can be significantly prolonged within inflamed tissue by cytokines, inflammatory mediators, and hypoxia. During screening experiments aimed at identifying the effect of the adhesive microenvironment on neutrophil survival, we found that VCAM-1 (CD106) was able to delay both spontaneous and Fas-induced apoptosis. VCAM-1-mediated survival was as efficient as that induced by the cytokine IFN-beta and provided an additive, increased delay in apoptosis when given in combination with IFN-beta. VCAM-1 delivered its antiapoptotic effect through binding the integrin alpha9beta1. The alpha9beta1 signaling pathway shares significant features with the IFN-beta survival signaling pathway, requiring PI3 kinase, NF-kappaB activation, as well as de novo protein synthesis, but the kinetics of NF-kappaB activation by VCAM-1 were slower and more sustained compared with IFN-beta. This study demonstrates a novel functional role for alpha9beta1 in neutrophil biology and suggests that adhesive signaling pathways provide an important extrinsic checkpoint for the resolution of inflammatory responses in tissues.

AB - According to the prevailing paradigm, neutrophils are short-lived cells that undergo spontaneous apoptosis within 24 hours of their release from the bone marrow. However, neutrophil survival can be significantly prolonged within inflamed tissue by cytokines, inflammatory mediators, and hypoxia. During screening experiments aimed at identifying the effect of the adhesive microenvironment on neutrophil survival, we found that VCAM-1 (CD106) was able to delay both spontaneous and Fas-induced apoptosis. VCAM-1-mediated survival was as efficient as that induced by the cytokine IFN-beta and provided an additive, increased delay in apoptosis when given in combination with IFN-beta. VCAM-1 delivered its antiapoptotic effect through binding the integrin alpha9beta1. The alpha9beta1 signaling pathway shares significant features with the IFN-beta survival signaling pathway, requiring PI3 kinase, NF-kappaB activation, as well as de novo protein synthesis, but the kinetics of NF-kappaB activation by VCAM-1 were slower and more sustained compared with IFN-beta. This study demonstrates a novel functional role for alpha9beta1 in neutrophil biology and suggests that adhesive signaling pathways provide an important extrinsic checkpoint for the resolution of inflammatory responses in tissues.

UR - http://www.scopus.com/inward/record.url?scp=31544442442&partnerID=8YFLogxK

U2 - 10.1182/blood-2005-07-2692

DO - 10.1182/blood-2005-07-2692

M3 - Article

C2 - 16223772

VL - 107

SP - 1178

EP - 1183

JO - Blood

JF - Blood

SN - 0006-4971

IS - 3

ER -