title: Inhalation of organic dusts and lipopolysaccharide increases gelatinolytic matrix metalloproteinases (MMPs) in the lungs of heaves horses.
abstract: We report the effects of mouldy hay/straw exposure, inhaled hay dust suspension (HDS) and inhaled lipopolysaccharide (LPS) on bronchoalveolar lavage fluid (BALF) gelatinolytic matrix metalloproteinase (MMP) levels and degree of activation in healthy (n = 6) and heaves- (previously termed chronic obstructive pulmonary disease) affected (n = 6 or 7) horses. Gelatinolytic MMPs in BALF were quantified by zymography, and gelatinases were shown by Western immunoblotting to be MMP-2 and MMP-9. Hay/straw and HDS challenges increased BALF total gelatinolytic activity only in heaves horses, with the majority of gelatinolytic activity comprising pro- and active MMP-9. The 5 h duration hay/straw challenge increased BALF gelatinolytic MMP activity in heaves horses at 5 and 24 h after the start of this challenge, with activity returning to baseline by Day 4. In contrast to hay/straw and HDS challenges, LPS inhalation increased BALF gelatinolytic MMP activity in both groups. For all challenges, absolute BALF neutrophil counts were highly significantly correlated (P<0.0001) with levels of proMMP-9 and active MMP-9, but not with levels of MMP-2 (P>0.05). As gelatinolytic MMPs are pro-inflammatory agents, they may contribute to lung dysfunction and tissue destruction in heaves horses exposed to airborne organic stable dusts.
authors.affiliation: Department of Virology and Epidemiology, National Veterinary and Food Research Institute, Faculty of Veterinary Medicine, University of Helsinki, Finland.
authors.forename: M
authors.initials: M
authors.lastname: Nevalainen
authors.forename: S M
authors.initials: SM
authors.lastname: Raulo
authors.forename: T J
authors.initials: TJ
authors.lastname: Brazil
authors.forename: R S
authors.initials: RS
authors.lastname: Pirie
authors.forename: T
authors.initials: T
authors.lastname: Sorsa
authors.forename: B C
authors.initials: BC
authors.lastname: McGorum
authors.forename: P
authors.initials: P
authors.lastname: Maisi
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D004391:Dust / Q000009:adverse effects*; D005260:Female; D006734:Horse Diseases / Q000201:enzymology* / Q000209:etiology / Q000473:pathology; D006736:Horses; D008070:Lipopolysaccharides / Q000009:adverse effects*; D008168:Lung / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D029424:Pulmonary Disease, Chronic Obstructive / Q000201:enzymology / Q000209:etiology / Q000473:pathology / Q000662:veterinary*
chemical_list: D004391:Dust; D008070:Lipopolysaccharides; D020782:Matrix Metalloproteinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9