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Cited by 367

The DOI matches its Crossref record; 39 of the 39 references it cites were found in a registry or an index.

Macrophage Metalloelastase Mediates Acute Cigarette Smoke–induced Inflammation via Tumor Necrosis Factor-α Release

Churg, Andrew, Wang, Rong D., Tai, Hsin, Wang, Xiaoshan, Xie, Changshi, Dai, Jin, Shapiro, Steven D., Wright, Joanne L.·2003·American Journal of Respiratory and Critical Care Medicine

Abstract

The cells and proteases that mediate cigarette smoke-induced emphysema are controversial, with evidence favoring either neutrophils and neutrophil-derived serine proteases or macrophages and macrophage-derived metalloproteases as the important effectors. We recently reported that both macrophage metalloelastase (MMP-12) and neutrophils are required for acute cigarette smoke-induced connective tissue breakdown, the precursor of emphysema. Here we show how these disparate observations can be linked. Both wild-type (MMP-12 +/+) mice and mice lacking MMP-12 (MMP-12 -/-) demonstrated rapid increases in whole-lung nuclear factor-kappaB activation and gene expression of proinflammatory cytokines after cigarette smoke exposure, indicating that a lack of MMP-12 does not produce a global failure to upregulate inflammatory mediators. However, only MMP-12 +/+ mice demonstrated increased whole-lung tumor necrosis factor-alpha (TNF-alpha) protein or release of TNF-alpha from cultured alveolar macrophages exposed to smoke in vitro. Levels of whole-lung E-selectin, an endothelial activation marker, were increased in only MMP-12 +/+ mice. These findings suggest that, acutely, MMP-12 mediates smoke-induced inflammation by releasing TNF-alpha from macrophages, with subsequent endothelial activation, neutrophil influx, and proteolytic matrix breakdown caused by neutrophil-derived proteases. TNF-alpha release may be a general mechanism whereby metalloproteases drive cigarette smoke-induced inflammation.

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Metadata

Authors
Churg, A., Wang, R. D., Tai, H., Wang, X., Xie, C., Dai, J., Shapiro, S. D., & Wright, J. L.
Venue
American Journal of Respiratory and Critical Care Medicine
Published
2003-04-15
Volume
167
Issue
8
Pages
1083-1089
ISSN
  • 1073-449X (ISSN-L)
  • 1535-4970
OpenAlex
W2168760383
Cited by
367
References
39
FWCI
24.52
Type
journal article
Language
en
Open access
closed

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CoChat. (2026). Citation check: Macrophage Metalloelastase Mediates Acute Cigarette Smoke–induced Inflammation via Tumor Necrosis Factor-α Release. https://app.cochat.ai/papers/10.1164/rccm.200212-1396oc
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Churg, A., Wang, R. D., Tai, H., Wang, X., Xie, C., Dai, J., Shapiro, S. D., & Wright, J. L. (2003). Macrophage Metalloelastase Mediates Acute Cigarette Smoke–induced Inflammation via Tumor Necrosis Factor-α Release. American Journal of Respiratory and Critical Care Medicine. https://doi.org/10.1164/rccm.200212-1396oc

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

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