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

TitleGene delivery of the elastase inhibitor elafin protects macrophages from neutrophil elastase-mediated impairment of apoptotic cell recognition.
Publication TypeJournal Article
Year of Publication2004
AuthorsHenriksen PA, Devitt A, Kotelevtsev Y, Sallenave J-M
JournalFEBS Lett
Volume574
Issue1-3
Pagination80-4
Date Published2004 Sep 10
ISSN0014-5793
KeywordsApoptosis, Genetic Vectors, Humans, Leukocyte Elastase, Macrophages, Proteinase Inhibitory Proteins, Secretory, Proteins
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.

DOI10.1016/j.febslet.2004.08.008
Alternate JournalFEBS Lett.
PubMed ID15358543