弹性蛋白酶抑制剂elafin的基因传递可保护巨噬细胞免受中性粒细胞弹性蛋白酶介导的凋亡细胞识别损伤。

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

作者信息

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

机构信息

Rayne Laboratory, MRC Centre for Inflammation Research, Edinburgh University Medical School, Teviot Place, Edinburgh EH8 9AG, UK.

出版信息

FEBS Lett. 2004 Sep 10;574(1-3):80-4. doi: 10.1016/j.febslet.2004.08.008.

DOI:10.1016/j.febslet.2004.08.008

PMID:15358543

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.

摘要

炎症的消退取决于巨噬细胞对凋亡细胞的识别和吞噬清除。凋亡细胞的受体对人中性粒细胞弹性蛋白酶（HNE）的降解敏感。我们在本研究中表明，HNE可切割巨噬细胞表面的CD14，从而降低对凋亡淋巴细胞（Mutu 1）的吞噬识别。通过一种改进的腺病毒介导的巨噬细胞转染方法，用HNE抑制剂elafin进行转染，我们证明elafin的过表达可防止CD14的切割，并恢复巨噬细胞对凋亡细胞的识别。这种对巨噬细胞进行基因改造的方法可用于在炎症条件下恢复对凋亡细胞的识别。