Apoptotic death of infiltrating cells in human cardiac allografts is regulated by IL-2, FASL, and FLIP

HA de Groot-Kruseman; CC Baan; PE Zondervan; RA de Weger; HGM Niesters; AHMM Balk; W Weimar

doi:10.1016/j.transproceed.2004.11.091

Apoptotic death of infiltrating cells in human cardiac allografts is regulated by IL-2, FASL, and FLIP

HA de Groot-Kruseman, CC Baan^*, PE Zondervan, RA de Weger, HGM Niesters, AHMM Balk, W Weimar

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Introduction. In vitro studies have shown that apoptotic cell death is triggered by a IL-2- dependent activation of the Fas-FasL pathway and that this pathway can be inhibited by FLIP.

Methods. To define whether FLIP regulates apoptotic death of graft infiltrating T-cells during IL-2-mediated rejection, we analyzed endomyocardial biopsies (EMB) from cardiac allograft recipients for CD3, DNA strand breaks (TUNEL assay), FLIP (mRNA and protein), and FasL mRNA expression.

Results. Apoptosis was present in CD3(+) T-cell infiltrates. The number of TUNEL-stained mononuclear cells was inversely correlated with FLIP mRNA expression levels (P = .09). FLIP protein was present in 5% to 10% of the infiltrating cells and was constitutively produced by cardiomyocytes irrespective of the rejection grade. Rejection biopsies had elevated IL-2 and FasL mRNA expression levels compared to the expression levels before and after acute rejection (P = .03 and P = .11), while FLIP mRNA expression levels were significantly decreased during rejection (P = .05).

Conclusion. Our results indicate that during the IL-2-induced rejection process, infiltrated T cells become more sensitive to apoptosis.

Original language	English
Pages (from-to)	3143-3148
Number of pages	6
Journal	Transplantation Proceedings
Volume	36
Issue number	10
DOIs	https://doi.org/10.1016/j.transproceed.2004.11.091
Publication status	Published - Dec 2004

Keywords

CLINICAL HEART-TRANSPLANTATION
MESSENGER-RNA EXPRESSION
ACUTE REJECTION
MEDIATED APOPTOSIS
T-LYMPHOCYTES
ACTIVATION
TOLERANCE
DISEASE
MODELS

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@article{22a95719552f4875897bcdad7a720d2d,

title = "Apoptotic death of infiltrating cells in human cardiac allografts is regulated by IL-2, FASL, and FLIP",

abstract = "Introduction. In vitro studies have shown that apoptotic cell death is triggered by a IL-2- dependent activation of the Fas-FasL pathway and that this pathway can be inhibited by FLIP.Methods. To define whether FLIP regulates apoptotic death of graft infiltrating T-cells during IL-2-mediated rejection, we analyzed endomyocardial biopsies (EMB) from cardiac allograft recipients for CD3, DNA strand breaks (TUNEL assay), FLIP (mRNA and protein), and FasL mRNA expression.Results. Apoptosis was present in CD3(+) T-cell infiltrates. The number of TUNEL-stained mononuclear cells was inversely correlated with FLIP mRNA expression levels (P = .09). FLIP protein was present in 5% to 10% of the infiltrating cells and was constitutively produced by cardiomyocytes irrespective of the rejection grade. Rejection biopsies had elevated IL-2 and FasL mRNA expression levels compared to the expression levels before and after acute rejection (P = .03 and P = .11), while FLIP mRNA expression levels were significantly decreased during rejection (P = .05).Conclusion. Our results indicate that during the IL-2-induced rejection process, infiltrated T cells become more sensitive to apoptosis.",

keywords = "CLINICAL HEART-TRANSPLANTATION, MESSENGER-RNA EXPRESSION, ACUTE REJECTION, MEDIATED APOPTOSIS, T-LYMPHOCYTES, ACTIVATION, TOLERANCE, DISEASE, MODELS",

author = "{de Groot-Kruseman}, HA and CC Baan and PE Zondervan and {de Weger}, RA and HGM Niesters and AHMM Balk and W Weimar",

year = "2004",

month = dec,

doi = "10.1016/j.transproceed.2004.11.091",

language = "English",

volume = "36",

pages = "3143--3148",

journal = "Transplantation Proceedings",

issn = "0041-1345",

publisher = "Elsevier",

number = "10",

}

TY - JOUR

T1 - Apoptotic death of infiltrating cells in human cardiac allografts is regulated by IL-2, FASL, and FLIP

AU - de Groot-Kruseman, HA

AU - Baan, CC

AU - Zondervan, PE

AU - de Weger, RA

AU - Niesters, HGM

AU - Balk, AHMM

AU - Weimar, W

PY - 2004/12

Y1 - 2004/12

N2 - Introduction. In vitro studies have shown that apoptotic cell death is triggered by a IL-2- dependent activation of the Fas-FasL pathway and that this pathway can be inhibited by FLIP.Methods. To define whether FLIP regulates apoptotic death of graft infiltrating T-cells during IL-2-mediated rejection, we analyzed endomyocardial biopsies (EMB) from cardiac allograft recipients for CD3, DNA strand breaks (TUNEL assay), FLIP (mRNA and protein), and FasL mRNA expression.Results. Apoptosis was present in CD3(+) T-cell infiltrates. The number of TUNEL-stained mononuclear cells was inversely correlated with FLIP mRNA expression levels (P = .09). FLIP protein was present in 5% to 10% of the infiltrating cells and was constitutively produced by cardiomyocytes irrespective of the rejection grade. Rejection biopsies had elevated IL-2 and FasL mRNA expression levels compared to the expression levels before and after acute rejection (P = .03 and P = .11), while FLIP mRNA expression levels were significantly decreased during rejection (P = .05).Conclusion. Our results indicate that during the IL-2-induced rejection process, infiltrated T cells become more sensitive to apoptosis.

AB - Introduction. In vitro studies have shown that apoptotic cell death is triggered by a IL-2- dependent activation of the Fas-FasL pathway and that this pathway can be inhibited by FLIP.Methods. To define whether FLIP regulates apoptotic death of graft infiltrating T-cells during IL-2-mediated rejection, we analyzed endomyocardial biopsies (EMB) from cardiac allograft recipients for CD3, DNA strand breaks (TUNEL assay), FLIP (mRNA and protein), and FasL mRNA expression.Results. Apoptosis was present in CD3(+) T-cell infiltrates. The number of TUNEL-stained mononuclear cells was inversely correlated with FLIP mRNA expression levels (P = .09). FLIP protein was present in 5% to 10% of the infiltrating cells and was constitutively produced by cardiomyocytes irrespective of the rejection grade. Rejection biopsies had elevated IL-2 and FasL mRNA expression levels compared to the expression levels before and after acute rejection (P = .03 and P = .11), while FLIP mRNA expression levels were significantly decreased during rejection (P = .05).Conclusion. Our results indicate that during the IL-2-induced rejection process, infiltrated T cells become more sensitive to apoptosis.

KW - CLINICAL HEART-TRANSPLANTATION

KW - MESSENGER-RNA EXPRESSION

KW - ACUTE REJECTION

KW - MEDIATED APOPTOSIS

KW - T-LYMPHOCYTES

KW - ACTIVATION

KW - TOLERANCE

KW - DISEASE

KW - MODELS

U2 - 10.1016/j.transproceed.2004.11.091

DO - 10.1016/j.transproceed.2004.11.091

M3 - Article

C2 - 15686714

SN - 0041-1345

VL - 36

SP - 3143

EP - 3148

JO - Transplantation Proceedings

JF - Transplantation Proceedings

IS - 10

ER -

Apoptotic death of infiltrating cells in human cardiac allografts is regulated by IL-2, FASL, and FLIP

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Keywords

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