Defenses of the Hamster Lung against Human Neutrophil and Porcine Pancreatic Elastase

Stone, Phillip J.; Lucey, Edgar C.; Calore, James D.; McMahon, Mary P.; Snider, Gordon L.; Franzblau, Carl

doi:10.1159/000195496

Cited by 22 publications

(15 citation statements)

References 18 publications

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“…Kinetic studies indicate that the exogenous elastase is removed from the lung within 24 hours (Stone et al, 1988). Our experimental results on the time-course of development of emphysema in wild-type mice after PPE treatment reveal that airspace enlargement continues for 10 or more days after the administered elastase is cleared from the lung (Fig.…”

Section: Discussionmentioning

confidence: 60%

Severity of Elastase-Induced Emphysema Is Decreased in Tumor Necrosis Factor-α and Interleukin-1β Receptor-Deficient Mice

Lucey

Keane

Kuang

et al. 2002

Laboratory Investigation

161

111

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SUMMARY:A single intratracheal dose of porcine pancreatic elastase, which is cleared from the lung by 24 hours, was administered to wild-type, IL-1␤ type 1 receptor-deficient, double TNF-␣ (type 1 and type 2) receptor-deficient, and combined TNF-␣ (type 1 receptor) plus IL-1␤ receptor-deficient mice. The mean linear intercept (Lm) of saline-treated mice was 32(3) m [mean(SE)]. For wild-type elastase-treated mice, Lm was 81(6) m at 21 days versus 52(5) m at 5 days after treatment, indicating that alveolar wall remodeling occurs long after the elastase injury. At 21 days, Lm values were 67(10), 62(3), and 39(5) m in elastase-treated mice deficient in the IL-1␤ receptor, double TNF-␣ receptors, and combined receptors, respectively. The level of apoptosis assessed by a terminal deoxynucleotidyl transferase-catalyzed in situ nick end-labeling assay was increased at 5 days after elastase treatment and was markedly and similarly attenuated in the IL-1␤, the double TNF-␣, and the combined receptor-deficient mice. Our results indicate that inflammatory mediators exacerbate elastase-induced emphysema. We estimate that in the combined TNF-␣ ϩ IL-1␤ receptor-deficient mice, inflammation accounts for about 80% of the emphysema that develops after elastase treatment; decreased apoptosis of lung cells likely contributes to decreased severity of emphysema. (Lab Invest 2002, 82:79 -85). P ulmonary emphysema is defined as abnormal enlargement of respiratory spaces with destruction of the alveolar walls. Experimental evidence supports the concept that alveolar units are damaged when activated macrophages and neutrophils elaborate proteases that degrade elastin and other structural proteins.The proinflammatory cytokines IL-1␤ and TNF-␣ are released during inflammatory reactions induced by infection or injury. These effecter substances have overlapping biologic functions, suggesting that they share some common signal transduction pathways (Dinarello, 1997;Kusano et al, 1998;Ledgerwood et al, 1999;Muegge et al, 1989; O' Neill and Greene, 1998;Stewart and Marsden, 1995).In experimental animals, IL-1␤ stimulates several components of the acute-phase response. The cytokine stimulates the expression of metalloproteinase and other enzymes involved in the degradation of connective tissue proteins (Kusano et al, 1998), and it also stimulates apoptosis (Dinarello, 1998). IL-1␤ utilizes a single signaling receptor to activate two IL-1 receptor-associated kinases (IRAK-1 and IRAK-2), to recruit TNF receptor-associated factor 6 (TRAF6) and activate nuclear factor-B (NF-B) (Cao et al, 1996). Activation of NF-B results in nuclear translocation and alterations in the rate of transcription of certain target genes (Baldwin, 1996;Gilmore, 1999). NF-B also either increases or decreases apoptosis depending on the cell type (Barkett and Gilmore, 1999). IL-1␤ affects gene transcription via several other transacting factors including transcription factor AP-1 proteins and CCAAT-enhancer binding proteins (C/EBP) (Muegge et al, 1989;Osborn et al, 1989).TNF...

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Section: Discussionmentioning

confidence: 60%

Severity of Elastase-Induced Emphysema Is Decreased in Tumor Necrosis Factor-α and Interleukin-1β Receptor-Deficient Mice

Lucey

Keane

Kuang

et al. 2002

Laboratory Investigation

161

111

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“…However, ␣ 2 -macroglobulin is produced mainly by hepatocytes in the liver, and only in small amounts by cells in the lungs (13). Moreover, a primary role of ␣ 2 -macroglobulin is to rapidly trap excess proteinases, but not to inactivate them, so proteases can still be released after binding ␣ 2 -macroglobulin (62,72). Unlike ␣ 2 -macroglobulin, ␣ 1 -AT is more likely to be a physiological inactivator of elastase.…”

Section: Discussionmentioning

confidence: 99%

Experimental progressive emphysema in BALB/cJ mice as a model for chronic alveolar destruction in humans

Limjunyawong

Craig

Lagassé

et al. 2015

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…PPE is cheap and easy to obtain, which makes it the most used protease. PPE and HNE have distinct primary endogenous inhibitors: α2-macroglobulin for PPE (α1-antitrypsin also may be effective) and α1-antitrypsin for HNE (Stone et al 1988), as well as distinct exogenous inhibitors, which may selectively inhibit these two proteases (Lai andDiamond 1990, Lafuma et al 1991).…”

Section: Comparison Of Elastase Modelsmentioning

confidence: 99%

Elastase-induced pulmonary emphysema: insights from experimental models

Antunes

Rocco

2011

An. Acad. Bras. Ciênc.

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Several distinct stimuli can be used to reproduce histological and functional features of human emphysema, a leading cause of disability and death. Since cigarette smoke is the main cause of emphysema in humans, experimental researches have attempted to reproduce this situation. However, this is an expensive and cumbersome method of emphysema induction, and simpler, more efficacious alternatives have been sought. Among these approaches, elastolytic enzymes have been widely used to reproduce some characteristics of human cigarette smoke-induced disease, such as: augmentation of airspaces, inflammatory cell influx into the lungs, and systemic inflammation. Nevertheless, the use of elastase-induced emphysema models is still controversial, since the disease pathways involved in elastase induction may differ from those occurring in smoke-induced emphysema. This indicates that the choice of an emphysema model may impact the results of new therapies or drugs being tested. The aim of this review is to compare the mechanisms of disease induction in smoke and elastase emphysema models, to describe the differences among various elastase models, and to establish the advantages and disadvantages of elastase-induced emphysema models. More studies are required to shed light on the mechanisms of elastase-induced emphysema.

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Defenses of the Hamster Lung against Human Neutrophil and Porcine Pancreatic Elastase

Cited by 22 publications

References 18 publications

Severity of Elastase-Induced Emphysema Is Decreased in Tumor Necrosis Factor-α and Interleukin-1β Receptor-Deficient Mice

Severity of Elastase-Induced Emphysema Is Decreased in Tumor Necrosis Factor-α and Interleukin-1β Receptor-Deficient Mice

Experimental progressive emphysema in BALB/cJ mice as a model for chronic alveolar destruction in humans

Elastase-induced pulmonary emphysema: insights from experimental models

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