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髓过氧化物酶介导的肺泡巨噬细胞激活:肺部炎症加重的一种模型

Alveolar macrophage activation by myeloperoxidase: a model for exacerbation of lung inflammation.

作者信息

Grattendick Ken, Stuart Rodney, Roberts Erin, Lincoln John, Lefkowitz Stanley S, Bollen Alex, Moguilevsky Nicole, Friedman Herman, Lefkowitz Doris L

机构信息

Department of Medical Microbiology and Immunology, University of South Florida, College of Medicine, Tampa 33612-4799, USA.

出版信息

Am J Respir Cell Mol Biol. 2002 Jun;26(6):716-22. doi: 10.1165/ajrcmb.26.6.4723.

DOI:10.1165/ajrcmb.26.6.4723
PMID:12034571
Abstract

Inflammation of the lung is characterized by the influx of increased numbers of various leukocytes including polymorphonuclear leukocyte (PMN) neutrophils. In addition to cells, numerous studies have pointed to the role of tumor necrosis factor-alpha in the inflammatory process. This study addresses a previously unrecognized interaction between neutrophil-derived myeloperoxidase (MPO) and resident alveolar macrophages (AMø). Rat AMø exposed to either enzymatically active recombinant MPO or enzymatically inactive MPO (iMPO) exhibited an increased respiratory burst (RB). When iMPO was employed, the enhancement of the RB was greater than that observed with MPO. Although the RB was greater with iMPO, macrophage (Mø)-mediated intracellular candidic activity was equivalent for both MPO and iMPO. It is known that pro- inflammatory cytokines contribute to the inflammatory process. When rat AMø were exposed to both forms of myeloperoxidase, iMPO demonstrated greater upregulation of cytokine genes as well as product. These data suggest that at the site of inflammation, neutrophil-derived MPO and iMPO stimulate AMø, resulting in an increased inflammatory and cytotoxic state, and thereby contributing to the general lung inflammatory response.

摘要

肺部炎症的特征是包括多形核白细胞(PMN)中性粒细胞在内的各种白细胞数量增加并流入。除了细胞外,大量研究指出肿瘤坏死因子-α在炎症过程中的作用。本研究探讨了中性粒细胞衍生的髓过氧化物酶(MPO)与驻留肺泡巨噬细胞(AMø)之间一种先前未被认识的相互作用。暴露于具有酶活性的重组MPO或无酶活性的MPO(iMPO)的大鼠AMø表现出呼吸爆发(RB)增加。当使用iMPO时,RB的增强大于使用MPO时观察到的增强。尽管iMPO的RB更大,但巨噬细胞(Mø)介导的细胞内念珠菌活性对于MPO和iMPO来说是相同的。已知促炎细胞因子有助于炎症过程。当大鼠AMø暴露于两种形式的髓过氧化物酶时,iMPO表现出细胞因子基因以及产物的更大上调。这些数据表明,在炎症部位,中性粒细胞衍生的MPO和iMPO刺激AMø,导致炎症和细胞毒性状态增加,从而促进肺部的一般炎症反应。

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