title: Nippostrongylus brasiliensis infection leads to the development of emphysema associated with the induction of alternatively activated macrophages.
abstract: Chronic obstructive pulmonary disease (COPD) is the 5(th) most prevalent disease worldwide leading to severe morbidity and mortality in developed countries. The disease is strongly associated with smoking, and can be characterized by progressive and irreversible deterioration in lung function and destruction of the lung parenchyma. We show here that infection with the hookworm Nippostrongylus brasiliensis results in deterioration in lung function, destruction of alveoli and long-term airways hyperresponsiveness, consistent with COPD and emphysema. N. brasiliensis infection leads to chronic low level hemorrhaging in the lung and the presence of hemosiderin-laden macrophages in the absence of an overt inflammatory infiltrate. Microarray analysis of gene expression in diseased lungs and quantitative RT-PCR analysis of purified macrophages revealed a state of prolonged tissue injury and the presence of alternatively activated macrophages producing MMP-12. Taken together, these data show that lung tissue damage caused by hookworm infection can result in the development of COPD and emphysema.
authors.affiliation: Molecular Biomedicine, Swiss Federal Institute of Technology, Zurich-Schlieren, Switzerland.
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Marsland
authors.forename: Michael
authors.initials: M
authors.lastname: Kurrer
authors.forename: Regina
authors.initials: R
authors.lastname: Reissmann
authors.forename: Nicola L
authors.initials: NL
authors.lastname: Harris
authors.forename: Manfred
authors.initials: M
authors.lastname: Kopf
mesh_terms: D000818:Animals; D000947:Antigens, Helminth / Q000276:immunology; D016535:Bronchial Hyperreactivity / Q000201:enzymology / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D002908:Chronic Disease; D008168:Lung / Q000201:enzymology / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D008262:Macrophage Activation / Q000276:immunology*; D008264:Macrophages / Q000201:enzymology / Q000276:immunology* / Q000469:parasitology; D053508:Matrix Metalloproteinase 12 / Q000096:biosynthesis / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009559:Nippostrongylus / Q000276:immunology*; D011656:Pulmonary Emphysema / Q000276:immunology* / Q000469:parasitology* / Q000473:pathology; D051381:Rats; D011917:Rats, Inbred Lew; D017206:Strongylida Infections / Q000201:enzymology / Q000276:immunology* / Q000473:pathology
chemical_list: D000947:Antigens, Helminth; D053508:Matrix Metalloproteinase 12