Gene delivery of the elastase inhibitor elafin protects macrophages from neutrophil elastase-mediated impairment of apoptotic cell recognition

Peter A Henriksen; Andrew Devitt; Yuri Kotelevtsev; Jean-Michel Sallenave

doi:10.1016/j.febslet.2004.08.008

Gene delivery of the elastase inhibitor elafin protects macrophages from neutrophil elastase-mediated impairment of apoptotic cell recognition

Peter A Henriksen, Andrew Devitt, Yuri Kotelevtsev, Jean-Michel Sallenave

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

Abstract

The resolution of inflammation is dependent on recognition and phagocytic removal of apoptotic cells by macrophages. Receptors for apoptotic cells are sensitive to degradation by human neutrophil elastase (HNE). We show in the present study that HNE cleaves macrophage cell surface CD14 and in so doing, reduces phagocytic recognition of apoptotic lymphocytic cells (Mutu 1). Using an improved method of adenovirus-mediated transfection of macrophages with the HNE inhibitor elafin, we demonstrate that elafin overexpression prevents CD14 cleavage and restores apoptotic cell recognition by macrophages. This approach of genetic modification of macrophages could be used to restore apoptotic cell recognition in inflammatory conditions.

Original language	English
Pages (from-to)	80-4
Number of pages	5
Journal	FEBS Letters
Volume	574
Issue number	1-3
DOIs	https://doi.org/10.1016/j.febslet.2004.08.008
Publication status	Published - 10 Sept 2004

Keywords / Materials (for Non-textual outputs)

Apoptosis
Genetic Vectors
Humans
Leukocyte Elastase/antagonists & inhibitors
Macrophages/drug effects
Proteinase Inhibitory Proteins, Secretory
Proteins/administration & dosage

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10.1016/j.febslet.2004.08.008

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title = "Gene delivery of the elastase inhibitor elafin protects macrophages from neutrophil elastase-mediated impairment of apoptotic cell recognition",

abstract = "The resolution of inflammation is dependent on recognition and phagocytic removal of apoptotic cells by macrophages. Receptors for apoptotic cells are sensitive to degradation by human neutrophil elastase (HNE). We show in the present study that HNE cleaves macrophage cell surface CD14 and in so doing, reduces phagocytic recognition of apoptotic lymphocytic cells (Mutu 1). Using an improved method of adenovirus-mediated transfection of macrophages with the HNE inhibitor elafin, we demonstrate that elafin overexpression prevents CD14 cleavage and restores apoptotic cell recognition by macrophages. This approach of genetic modification of macrophages could be used to restore apoptotic cell recognition in inflammatory conditions.",

keywords = "Apoptosis, Genetic Vectors, Humans, Leukocyte Elastase/antagonists & inhibitors, Macrophages/drug effects, Proteinase Inhibitory Proteins, Secretory, Proteins/administration & dosage",

author = "Henriksen, {Peter A} and Andrew Devitt and Yuri Kotelevtsev and Jean-Michel Sallenave",

year = "2004",

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doi = "10.1016/j.febslet.2004.08.008",

language = "English",

volume = "574",

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journal = "FEBS Letters",

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T1 - Gene delivery of the elastase inhibitor elafin protects macrophages from neutrophil elastase-mediated impairment of apoptotic cell recognition

AU - Henriksen, Peter A

AU - Devitt, Andrew

AU - Kotelevtsev, Yuri

AU - Sallenave, Jean-Michel

PY - 2004/9/10

Y1 - 2004/9/10

N2 - The resolution of inflammation is dependent on recognition and phagocytic removal of apoptotic cells by macrophages. Receptors for apoptotic cells are sensitive to degradation by human neutrophil elastase (HNE). We show in the present study that HNE cleaves macrophage cell surface CD14 and in so doing, reduces phagocytic recognition of apoptotic lymphocytic cells (Mutu 1). Using an improved method of adenovirus-mediated transfection of macrophages with the HNE inhibitor elafin, we demonstrate that elafin overexpression prevents CD14 cleavage and restores apoptotic cell recognition by macrophages. This approach of genetic modification of macrophages could be used to restore apoptotic cell recognition in inflammatory conditions.

AB - The resolution of inflammation is dependent on recognition and phagocytic removal of apoptotic cells by macrophages. Receptors for apoptotic cells are sensitive to degradation by human neutrophil elastase (HNE). We show in the present study that HNE cleaves macrophage cell surface CD14 and in so doing, reduces phagocytic recognition of apoptotic lymphocytic cells (Mutu 1). Using an improved method of adenovirus-mediated transfection of macrophages with the HNE inhibitor elafin, we demonstrate that elafin overexpression prevents CD14 cleavage and restores apoptotic cell recognition by macrophages. This approach of genetic modification of macrophages could be used to restore apoptotic cell recognition in inflammatory conditions.

KW - Apoptosis

KW - Genetic Vectors

KW - Humans

KW - Leukocyte Elastase/antagonists & inhibitors

KW - Macrophages/drug effects

KW - Proteinase Inhibitory Proteins, Secretory

KW - Proteins/administration & dosage

U2 - 10.1016/j.febslet.2004.08.008

DO - 10.1016/j.febslet.2004.08.008

M3 - Article

C2 - 15358543

SN - 0014-5793

VL - 574

SP - 80

EP - 84

JO - FEBS Letters

JF - FEBS Letters

IS - 1-3

ER -

Gene delivery of the elastase inhibitor elafin protects macrophages from neutrophil elastase-mediated impairment of apoptotic cell recognition

Abstract

Keywords / Materials (for Non-textual outputs)

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