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 journalArticle

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 inbibitor 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. (C) 2004 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
Original languageEnglish
Pages (from-to)80-84
Number of pages5
JournalFEBS Letters
Volume574
Issue number1-3
Early online date14 Aug 2004
DOIs
Publication statusPublished - 10 Sep 2004

Keywords

  • neutrophil elastase
  • elafin
  • macrophage
  • apoptosis
  • adenovirus
  • gene therapy

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