Requirement for Macrophage Elastase for Cigarette Smoke-Induced Emphysema in Mice

Hautamaki, R. Dean; Kobayashi, Dale K.; Senior, Robert M.; Shapiro, Steven D.

doi:10.1126/science.277.5334.2002

Cited by 1,344 publications

(1,149 citation statements)

References 23 publications

Supporting

Mentioning

1,072

Contrasting

Unclassified

Order By: Relevance

“…These inflammatory cells express enzymes that exhibit elastolytic activity. MMP‐12, also known as macrophage elastase, is involved in the development of emphysema, and a targeted deletion of MMP‐12 confers resistance to cigarette smoke‐induced emphysema (Hautamaki et al, 1997). Furthermore, many pro‐inflammatory cytokines and MMPs are incorporated in SASP in humans and mice (Freund et al, 2010) and are elevated in senescent cells as well as in aged tissue.…”

Section: Resultsmentioning

confidence: 99%

“…This inflammation is an essential step in the development of PPE‐induced emphysema, and the suppression of alveolar inflammation has been shown to be sufficient at preventing PPE‐induced alveolar collapse (Shapiro et al, 2003; Ueno et al, 2015). In addition, the inactivation of MMP‐12 or neutrophil elastase confers resistance to cigarette smoke‐induced emphysema in mice (Hautamaki et al, 1997; Shapiro et al, 2003). Our results suggest that the presence of p19 ARF ‐expressing cells facilitates the accumulation of macrophages, which occurs at a relatively early stage after PPE challenge.…”

Section: Discussionmentioning

confidence: 99%

“…Macrophages are predominant inflammatory cells in lung tissues, and their number increases in emphysema (Rodriguez, White, Senior, & Levine, 1977). Matrix metalloproteinase (MMP)‐12, also known as macrophage elastase, is required for the development of cigarette smoke‐induced emphysema in mice (Hautamaki, Kobayashi, Senior, & Shapiro, 1997), and the inhibition of macrophage recruitment or induction of apoptosis in alveolar macrophages was found to suppress alveolar collapse in an elastase‐induced emphysema model (Houghton et al, 2006; Ueno et al, 2015). Neutrophils are also known to contribute to the pathology of emphysema, and the inactivation of neutrophil elastase was shown to confer resistance in a mouse emphysema model (Shapiro et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Elimination of p19^ARF‐expressing cells protects against pulmonary emphysema in mice

et al. 2018

View full text Add to dashboard Cite

Senescent cells accumulate in tissues during aging and are considered to underlie several aging‐associated phenotypes and diseases. We recently reported that the elimination of p19ARF‐expressing senescent cells from lung tissue restored tissue function and gene expression in middle‐aged (12‐month‐old) mice. The aging of lung tissue increases the risk of pulmonary diseases such as emphysema, and cellular senescence is accelerated in emphysema patients. However, there is currently no direct evidence to show that cellular senescence promotes the pathology of emphysema, and the involvement of senescence in the development of this disease has yet to be clarified. We herein demonstrated that p19ARF facilitated the development of pulmonary emphysema in mice. The elimination of p19ARF‐expressing cells prevented lung tissue from elastase‐induced lung dysfunction. These effects appeared to depend on reduced pulmonary inflammation, which is enhanced after elastase stimulation. Furthermore, the administration of a senolytic drug that selectively kills senescent cells attenuated emphysema‐associated pathologies. These results strongly suggest the potential of senescent cells as therapeutic/preventive targets for pulmonary emphysema.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Elimination of p19^ARF‐expressing cells protects against pulmonary emphysema in mice

et al. 2018

View full text Add to dashboard Cite

show abstract

“…For example, MMP9 contributes to inflammation in mouse models of stroke, heart attack, Alzheimer's disease, some aspects of asthma and other lung inflammatory conditions, aortic aneurysms and autoimmune encephalomyelitis 9,[106][107][108][109][110] ; however, it functions as an anti-inflammatory agent in models of inflammatory skin and kidney diseases 89,111,112 . Current data indicate that MMP12 contributes to emphysema 113,114 , whereas MMP3 and MMP9 contribute to skin inflammatory conditions 89,115 . By contrast, MMP8 protects against skin inflammatory responses 104 and MMP2 protects against inflammation of the brain and spinal cord 116 .…”

Section: Mmps In Human Inflammatory Disease Modelsmentioning

confidence: 93%

Matrix metalloproteinases and the regulation of tissue remodelling

Page-McCaw

Ewald

Werb

2007

Nat Rev Mol Cell Biol

2,560

2,180

View full text Add to dashboard Cite

Matrix metalloproteinases (MMPs) were discovered because of their role in amphibian metamorphosis, yet they have attracted more attention because of their roles in disease. Despite intensive scrutiny in vitro, in cell culture and in animal models, the normal physiological roles of these extracellular proteases have been elusive. Recent studies in mice and flies point to essential roles of MMPs as mediators of change and physical adaptation in tissues, whether developmentally regulated, environmentally induced or disease associated.The founding member of the matrix metalloproteinase (MMP) family, collagenase, was identified in 1962 by Gross and Lapiere, who found that tadpole tails during metamorphosis contained an enzyme that could degrade fibrillar collagen 1,2 . Subsequently, an interstitial collagenase, collagenase-1 or MMP1, was found in diseased skin and synovium 3 . In vitro, MMP1 initiates degradation of native fibrillar collagens, crucial components of vertebrate extracellular matrix (ECM), by cleaving the peptide bond between Gly775-Ile776 or Gly775-Lys776 in native type I, II or III collagen molecules 3,4 . Further research led to the discovery of a family of structurally related proteinases (23 in human, 24 in mice), now referred to as the MMP family.Interest in MMPs increased in the late 1960s and early 1970s following observations that MMPs are upregulated in diverse human diseases including rheumatoid arthritis and cancer. Importantly, high levels of MMPs often correlated with poor prognosis in human patients (reviewed in REF. 5 ). However, recent clinical data indicate that the relationship between § These authors contributed equally to this paper. Competing interests statementThe authors declare no competing financial interests. DATABASESThe following terms in this article are linked online to: Entrez Genome: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=gene DmMmp1 | DmMmp2 NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptMMPs and disease is not simple; for example, increased MMP activity can enhance tumour progression or can inhibit it (reviewed in REF. 6 ). This complex relationship between MMP expression and cancer has increased the basic and clinical interest in understanding MMP function in vivo, but it has also focused attention on MMPs and pathology, and relatively less attention has been focused on the normal roles of these enzymes. MMP proteolysisMMPs are members of the metzincin group of proteases, which are named after the zinc ion and the conserved Met residue at the active site 11,12 . Recent work has generated a unified peptidase nomenclature 13 Functions of MMP proteolysisHistorically, MMPs were thought to function mainly as enzymes that degrade structural components of the ECM. However, MMP proteolysis can create space for cells to migrate, can produce specific substrate-cleavage fragments with independent biological activity, can MMPs in bone modelling and remodellingBone is an important site of ongoing tissue remodelling during development...

show abstract

“…Diseases characterized by loss of elastic fibers, such as emphysema, are usually viewed in terms of an imbalance between elastases and their inhibitors 8,25,26 . Given our finding that LOXL1-dependent elastin polymer deposition has an active role in elastic fiber homeostasis, this theory might be updated to include an imbalance between degradation and renewal as well.…”

mentioning

confidence: 99%

Elastic fiber homeostasis requires lysyl oxidase–like 1 protein

et al. 2004

View full text Add to dashboard Cite

Requirement for Macrophage Elastase for Cigarette Smoke-Induced Emphysema in Mice

Cited by 1,344 publications

References 23 publications

Elimination of p19^ARF‐expressing cells protects against pulmonary emphysema in mice

Elimination of p19^ARF‐expressing cells protects against pulmonary emphysema in mice

Matrix metalloproteinases and the regulation of tissue remodelling

Elastic fiber homeostasis requires lysyl oxidase–like 1 protein

Contact Info

Product

Resources

About

Requirement for Macrophage Elastase for Cigarette Smoke-Induced Emphysema in Mice

Cited by 1,344 publications

References 23 publications

Elimination of p19ARF‐expressing cells protects against pulmonary emphysema in mice

Elimination of p19ARF‐expressing cells protects against pulmonary emphysema in mice

Matrix metalloproteinases and the regulation of tissue remodelling

Elastic fiber homeostasis requires lysyl oxidase–like 1 protein

Contact Info

Product

Resources

About

Elimination of p19^ARF‐expressing cells protects against pulmonary emphysema in mice

Elimination of p19^ARF‐expressing cells protects against pulmonary emphysema in mice