Role of metalloelastase in a model of allergic lung responses induced by cockroach allergen.

Abstract

Our laboratory and others have shown an important role of metalloelastase (MMP-12) in the pathogenesis of acute and chronic lung injury. Because chronic asthma is characterized by airway inflammation and alterations in the airway extracellular matrix, we explored the role of metalloelastase in a model of allergic airway inflammation induced by cockroach antigen (CRA). Using MMP-12-deficient mice we found a significant reduction in CRA-induced inflammatory injury, as evidenced by fewer peribronchial leukocytes, significantly less protein in the bronchoalveolar lavage (BAL) fluid, and a significant reduction in the number of infiltrating neutrophils, eosinophils, and macrophages, relative to wild-type mice. Although we did not find a significant reduction in the number of T cells in the injured MMP-12-deficient animals as compared to controls, levels of the chemotactic factors interleukin-5, macrophage inflammatory protein-1 alpha, monocyte chemoattractant protein-1, thymus activation regulated chemokine, and the proinflammatory cytokine tumor necrosis factor-alpha were significantly reduced in the bronchoalveolar lavage fluid of CRA-challenged MMP-12-deficient mice, relative to CRA-challenged control animals. These studies indicate that MMP-12 plays an important proinflammatory role in the development of allergic inflammation in the CRA model. Alterations in the levels of chemotactic factors and other proinflammatory cytokines in the MMP-12-deficient mice may underlie the decrease in leukocyte recruitment into inflamed lungs.

• Authors: Roscoe L Warner, Nicholas W Lukacs, Steven D Shapiro, Narasimharao Bhagarvathula, Kamalakar C Nerusu, James Varani, Kent J Johnson
• Journal: The American journal of pathology (Am J Pathol) Vol. 165 Issue 6 Pg. 1921-30 (Dec 2004) ISSN: 0002-9440 [Print] United States
• PMID: 15579436 (Publication Type: Comparative Study, Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Allergens
• Antigens, Plant
• Chemokines
• Cytokines
• allergen CRa, cockroach
• Metalloendopeptidases
• Matrix Metalloproteinase 12

Topics

• Allergens (immunology)
• Animals
• Antigens, Plant
• Bronchial Hyperreactivity (enzymology, etiology, immunology)
• Bronchoalveolar Lavage
• Chemokines (metabolism)
• Cockroaches (immunology)
• Cytokines (metabolism)
• Disease Models, Animal
• Eosinophils (immunology, pathology)
• Leukocytes (pathology)
• Lung (enzymology, pathology)
• Macrophages (immunology, pathology)
• Matrix Metalloproteinase 12
• Metalloendopeptidases (physiology)
• Mice
• Mice, Knockout
• Neutrophils (immunology, pathology)