Immunolocalization of elastase in human emphysematous lungs.

Damiano, V.V.; Tsang, A; Kucich, Umberto; Abrams, William R.; Rosenbloom, J.; Kimbel, Philip; M, Fallahnejad; Weinbaum, George

doi:10.1172/jci112600

Cited by 166 publications

(64 citation statements)

References 36 publications

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“…It is noteworthy in this respect that HLE has been found in association with interstitial elastin in human emphysematous lungs [118]. These data suggest that elastinbound HLE retains catalytic activity in vivo, and may thereby contribute to the pathogenesis of pulmonary emphysema.…”

Section: Serine Proteinasesmentioning

confidence: 82%

The cell biology of leukocyte-mediated proteolysis

Owen

Campbell

1999

Journal of Leukocyte Biology

383

399

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Leukocyte-derived proteinases have the capacity to degrade every component of the extracellular matrix, and thereby play fundamental roles in physiological processes. However, if the activity of these proteinases is uncontrolled or dysregulated, they have the capacity to contribute to tissue injury that potentially affects every organ in the body. Although there is a substantial literature on structure and activity of these proteinases when they are free in solution, until recently there has been little information about the cell biology of proteinases and their inhibitors. Recent studies, however, have identified several mechanisms by which inflammatory cells can degrade extracellular proteins in a milieu that contains high-affinity proteinase inhibitors. J. Leukoc. Biol. 65: 137-150; 1999.

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Section: Serine Proteinasesmentioning

confidence: 82%

The cell biology of leukocyte-mediated proteolysis

Owen

Campbell

1999

Journal of Leukocyte Biology

383

399

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“…The excessive activity of NE serves as a hallmark of the elastase/anti-elastase imbalance in the emphysematous lung (4,34,35,37). We describe in this article how NE, by releasing EGF-like and TGF-␣-like EGFR ligands, transactivates the EGFR/MEK/ERK cascade that signals to destabilize tropoelastin mRNA and thereby downregulates elastogenesis in a RFL-6 lung fibroblast cell culture model.…”

Section: Discussionmentioning

confidence: 98%

Neutrophil elastase-initiated EGFR/MEK/ERK signaling counteracts stabilizing effect of autocrine TGF-β on tropoelastin mRNA in lung fibroblasts

DiCamillo

Yang²,

Toselli³

et al. 2006

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…[7] It could be argued that the measurement of elastolytic activity in induced sputum may not accurately assess the activity in the interstitium, the site of extracellular matrix degradation in emphysema. However, the study which showed neutrophil elastase in close association with elastic fibers in the interstitium, in an amount that correlates with the severity of emphysema, [33] has been questioned in another study, that failed to reproduce these findings. [34] Furthermore, homogenates of lung removed in volume reduction surgery revealed significant elevations in MMP-9, with no significant increase in neutrophil elastase.…”

Section: Discussionmentioning

confidence: 97%

Markers of emphysema are associated with more severe chronic obstructive pulmonary disease

Boschetto

Quintavalle

Zeni

et al. 2006

Respiratory Medicine: COPD Update

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Background:The predominant emphysema phenotype is associated with more severe airflow limitation in patients with chronic obstructive pulmonary disease (COPD). We investigated whether COPD patients with or without quantitatively HRCT scan-documented emphysema have different COPD severity, as assessed by BODE (body mass index, airflow obstruction, dyspnea, exercise performance) Index and inspiratory capacity-to-total lung capacity ratio (IC/TLC), and by different biological markers of lung parenchymal destruction. Methods: We examined 26 outpatients with COPD and 8 healthy nonsmokers. Each subject underwent HRCT scan, pulmonary function tests, cell counts and measurements of neutrophil elastase, matrix metalloproteinase (MMP)-9 and tissue inhibitor of metalloproteinase (TIMP)-1 in induced sputum, as well as measurement of desmosine, a marker of elastin degradation in urine, plasma and sputum. Results: As compared with subjects without HRCT documented emphysema and controls, patients with HRCT scan-documented emphysema had higher BODE Index and lower IC/TLC. Forced expiratory volume in one second (FEV 1 ), FEV 1 /forced vital capacity ratio, and carbon monoxide transfer coefficient were lower, whereas the number of eosinophils, MMP-9 and the MMP-9/TIMP-1 ratio in sputum were higher in patients with emphysema. In COPD patients, the number of sputum eosinophils was the biological variable that correlated positively with the HRCT score of emphysema (p = 0.04). Conclusions:These results suggest that COPD associated with HRCT scan documented emphysema is characterized by more severe lung function impairment, more intense airway inflammation, and, possibly, more serious systemic dysfunctioning, as compared with COPD not associated with HRCT scan-documented emphysema.Word counts: 242 Key words: chronic obstructive pulmonary disease, emphysema, biological markers, outcomes. INTRODUCTIONChronic obstructive pulmonary disease (COPD) is characterized by the progressive development of airflow limitation that is not fully reversible.[1] Chronic airflow limitation may be caused by increased resistance of the small conducting airways and increased compliance of the lung due to emphysema.[1] We have previously shown that COPD patients with HRCT-documented emphysema have more severe airflow limitation.[2] Now we hypothesize that COPD patients with emphysema, as quantitatively assessed by HRCT, may be associated with more severe disease and may be characterized by biological markers of lung parenchymal destruction, measurable by noninvasive methods. The BODE (body mass index, airflow obstruction, dyspnea, exercise performance) Index and the inspiratory capacity-to-total lung capacity ratio (IC/TLC) have been recently demonstrated to grade properly the severity of COPD, as a systemic and respiratory disease, and to predict the outcome in these patients. [3][4] The higher the BODE Index and the lower the IC/TLC ratio, the higher is the risk of death from any cause and respiratory causes in subjects with COPD. There have been...

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Immunolocalization of elastase in human emphysematous lungs.

Abstract: The current working hypothesis concerning the pathogenesis of humab pulmonary emphysema proposes

Cited by 166 publications

References 36 publications

The cell biology of leukocyte-mediated proteolysis

The cell biology of leukocyte-mediated proteolysis

Neutrophil elastase-initiated EGFR/MEK/ERK signaling counteracts stabilizing effect of autocrine TGF-β on tropoelastin mRNA in lung fibroblasts

Markers of emphysema are associated with more severe chronic obstructive pulmonary disease

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