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.
authors.affiliation: Rayne Laboratory, MRC Centre for Inflammation Research, Edinburgh University Medical School, Teviot Place, Edinburgh EH8 9AG, UK.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Henriksen
authors.forename: Andrew
authors.initials: A
authors.lastname: Devitt
authors.forename: Yuri
authors.initials: Y
authors.lastname: Kotelevtsev
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Sallenave
mesh_terms: D017209:Apoptosis; D005822:Genetic Vectors; D006801:Humans; D019272:Leukocyte Elastase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects*; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins / Q000008:administration & dosage* / Q000494:pharmacology
chemical_list: D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins; D019272:Leukocyte Elastase