Increase in macrophage elastase (MMP-12) in lungs from patients with chronic obstructive pulmonary disease

Molet, Sophie; Belleguic, Chantal; Léna, H.; Germain, Nicolas; Bertrand, Claude; Shapiro, Steven D.; Planquois, Jean-Michel; Delaval, P.; Lagente, Vincent

doi:10.1007/s00011-004-1319-4

Cited by 205 publications

(130 citation statements)

References 19 publications

(33 reference statements)

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“…In this study, our data demonstrate that over-activation of TGFβ1 together with MMP2 and MMP12 expression at the mRNA level in WT mice, which is partly in accordance with the previous reports that increased MMPs at the protein level were seen in patients with emphysema [27,28] , have tissue destructive and fibrotic effects depending on the location (either in parenchyma or in airways) [31] . It should be pointed out that the current study was based on a short-term exposure model.…”

Section: Discussionsupporting

confidence: 92%

“…Elias and colleagues have provided evidence that these enzymes may be regulated by proximal immune events through a Th1 cell-or IFNγ-dependent manner [26] . T cells, particularly CD8+ T cells, accumulate in the lungs of patients with COPD and generate signals such as CXCL10/ IP-10 that promote MMP12 production by macro phages [27,28] . Moreover, CXCR3 expressed by human T cells and macrophages is required for MMP12 secretion in response to IP-10/Mig stimulation [24] .…”

Section: Discussionmentioning

confidence: 99%

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Chemokine receptor CXCR3 is important for lung tissue damage and airway remodeling induced by short-term exposure to cigarette smoking in mice

et al. 2010

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Aim: To investigate the role of chemokine receptor CXCR3 in cigarette smoking (CS)-induced pulmonary damage. Methods: CXCR3 knockout (CXCR3-/-) mice were used. Differences in airspace enlargement, mRNA expression of matrix metalloproteinases (MMPs), transforming growth factor (TGF) β1, CXCL10 in lung homogenates, and CXCL10 content in bronchoalveolar lavage (BAL) fluids and homogenates were compared between CXCR3-/-mice and wild-type (WT) mice three days after three-day CS exposures. Results: The linear intercept was significantly less in CXCR3-/-mice than in WT mice (30.1±0.9 µm vs 40.3±2.4 µm, P<0.01). Morphologically, collagen was deposited less around airways and vessels in CXCR3-/-mice. The lung hydroxyproline content was significantly lower in CXCR3-/-mice than in WT mice (6.0±1.0 µg/mL vs 12.0±1.6 µg/mL, P<0.05). Profoundly lower mRNA expression of MMP2, MMP12, TGFβ1, and CXCL10 was seen in lung homogenates from CXCR3-/-mice. CXCL10 concentrations in BAL fluid and lung homogenates were significantly lower in CXCR3-/-mice than in WT mice (BAL fluid: 19.3±1.4 pg/mL vs 24.8±1.6 pg/mL, P<0.05; lung homogenates: 76.6±7.0 pg/mL vs 119.5±15.9 pg/mL, P<0.05). Conclusion: CXCR3 is important in mediating lung tissue damage and airway remodeling following a short-term CS insult, possibly through up-regulation of CXCL10 and inducement of mRNA expression of MMPs. Targeting CXCR3 may be helpful for prevention of CSinduced pulmonary pathology.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Chemokine receptor CXCR3 is important for lung tissue damage and airway remodeling induced by short-term exposure to cigarette smoking in mice

et al. 2010

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“…These cells preferentially traffic to sites of inflammation. The preferential recruitment of these proinflammatory cells provides an abundant source of a number of proteases including cathepsins K, L, and S, as well as MMPs-1, -2, -9, and -12, and the production of these proteases appears to be elevated in lung macrophages in patients with COPD both in vivo and ex vivo (57)(58)(59)(60)(61).…”

Section: The Nature Of Inflammatory and Cellular Infiltration In Copdmentioning

confidence: 99%

New Concepts in the Pathobiology of Chronic Obstructive Pulmonary Disease

Kim¹,

Rogers²,

Criner³

2008

Proceedings of the American Thoracic Society

173

120

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Chronic obstructive pulmonary disease (COPD) is characterized by an abnormal persistent inflammatory response to cigarette smoke. This noxious insult leads to emphysema and airway remodeling, manifested by squamous and mucous metaplasia of the epithelium, smooth muscle hypertrophy, and airway wall fibrosis. These pathologic abnormalities interact synergistically to cause progressive airflow obstruction. Although it has been accepted that the spectrum of COPD is vast, the reasons for the development of different phenotypes from the same exposure to cigarette smoke have not been determined. Furthermore, it is becoming increasingly clear that airways disease and emphysema often coexist in many patients, even with a clear clinical phenotype of either emphysema or chronic bronchitis. Recent studies have focused on the nature of the inflammatory response to cigarette smoke, the inflammatory cell lines responsible for COPD pathogenesis, and new biomarkers for disease activity and progression. New cytokines are being discovered, and the complex interactions among them are being unraveled. The inflammatory biomarker that has received the most attention is Creactive protein, but new ones that have caught our attention are interleukin (IL)-6, tumor necrosis factor-a, IL-8, and IL-10. Further research should focus on how these new concepts in lung inflammation interact to cause the various aspects of COPD pathology.

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“…Enhanced MMP-12 activity was also detected in BAL fluids from patients with COPD in comparison with control subjects. The study in question demonstrated that COPD patients produce greater quantities of MMP-12 than controls, which may be a critical step in the pathogenesis of COPD and emphysema (23). Studies using MMP-12 knock-out (KO) mice have demonstrated that macrophage recruitment in lungs and emphysema induced by long-term exposure to cigarette smoke were linked to MMP-12 (24).…”

Section: Role Of Mmp In the Development Of Airway Inflammation In Chrmentioning

confidence: 99%

Role of matrix metalloproteinases in the development of airway inflammation and remodeling

Lagente

Manoury

Nénan

et al. 2005

Braz J Med Biol Res

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144

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Increase in macrophage elastase (MMP-12) in lungs from patients with chronic obstructive pulmonary disease

Abstract: This study demonstrated that COPD patients produce greater quantities of MMP-12 than controls, which may be a critical step in the pathogenesis of COPD and emphysema.

Cited by 205 publications

References 19 publications

Chemokine receptor CXCR3 is important for lung tissue damage and airway remodeling induced by short-term exposure to cigarette smoking in mice

Chemokine receptor CXCR3 is important for lung tissue damage and airway remodeling induced by short-term exposure to cigarette smoking in mice

New Concepts in the Pathobiology of Chronic Obstructive Pulmonary Disease

Role of matrix metalloproteinases in the development of airway inflammation and remodeling

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