Role of metalloelastase in a model of allergic lung responses induced by cockroach allergen.
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.
Warner
Roscoe L
RL
Department of Pathology, The University of Michigan, 1301 Catherine Rd., Box 0602, Ann Arbor, MI 48109, USA.
Lukacs
Nicholas W
NW
Shapiro
Steven D
SD
Bhagarvathula
Narasimharao
N
Nerusu
Kamalakar C
KC
Varani
James
J
Johnson
Kent J
KJ
D000485:Allergens / Q000276:immunology*; D000818:Animals; D052179:Antigens, Plant; D016535:Bronchial Hyperreactivity / Q000201:enzymology* / Q000209:etiology / Q000276:immunology; D018893:Bronchoalveolar Lavage; D018925:Chemokines / Q000378:metabolism; D003058:Cockroaches / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004804:Eosinophils / Q000276:immunology / Q000473:pathology; D007962:Leukocytes / Q000473:pathology; D008168:Lung / Q000201:enzymology* / Q000473:pathology; D008264:Macrophages / Q000276:immunology / Q000473:pathology; D053508:Matrix Metalloproteinase 12; D008666:Metalloendopeptidases / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009504:Neutrophils / Q000276:immunology / Q000473:pathology
D000485:Allergens; D052179:Antigens, Plant; D018925:Chemokines; D016207:Cytokines; C060835:allergen CRa, cockroach; D008666:Metalloendopeptidases; D053508:Matrix Metalloproteinase 12