Dose responses to inhalation of endotoxin, hay dust suspension and Aspergillus fumigatus extract in horses as measured by levels and activation of matrix metalloproteinase-9.
BACKGROUND
Airway matrix metalloproteinases (MMPs) increase after endotoxin (LPS) exposure, but there are no reports describing dose-dependent increases or activation following exposure.


OBJECTIVE
To study matrix metalloproteinase-9 (MMP-9) and -2 (MMP-2) responses in bronchoalveolar lavage fluid (BALF) from heaves-susceptible and control horses following inhalation of hay dust suspension (HDS), LPS and Aspergillus fumigatus extract (AFE).


METHODS
Heaves-susceptible (n = 7) and control (n = 6) horses received inhalation challenges with 3 different doses of HDS and LPS. Heaves-susceptible horses (n = 6) also received 3 different doses of AFE and one dose of AFE depleted of endotoxin (AFE-LPS). BALF collected following inhalation challenges was analysed using gelatin zymography. Gelatinolytic bands were identified as complex, pro-MMP-9, active MMP-9, pro-MMP-2 and active MMP-2 based on molecular weights.


RESULTS
Each challenge substance induced a dose-dependent elevation in gelatinolytic activity. The dose-dependency was most evident for pro-MMP-9 and total MMP-9 levels in heaves-susceptible horses following LPS challenges.


CONCLUSIONS
There is a dose-dependent elevation in MMP-9 in BALF of heaves-susceptible and control horses following inhalation challenge with organic dust and some of its components, elevation being more marked in heaves-susceptible horses. Organic dust components vary in their pro-inflammatory potential.


CONCLUSIONS
This study supports the role of MMPs in the pathogenesis of heaves and highlights the potential value of protease inhibitors in attenuating the airway inflammatory response to inhaled organic dust.
Simonen-Jokinen
T
T
Department of Clinical Veterinary Sciences, Pharmacology and Toxicology, Faculty of Veterinary Medicine, University of Helsinki, Finland.
Pirie
R S
RS
McGorum
B
B
Maisi
P
P
D000818:Animals; D001232:Aspergillus fumigatus / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D016022:Case-Control Studies; D004306:Dose-Response Relationship, Immunologic; D004391:Dust / Q000276:immunology*; D004731:Endotoxins / Q000633:toxicity*; D004789:Enzyme Activation; D005260:Female; D006734:Horse Diseases / Q000201:enzymology* / Q000276:immunology; D006736:Horses; D019570:Inhalation Exposure; D008070:Lipopolysaccharides / Q000633:toxicity; D008168:Lung / Q000201:enzymology / Q000378:metabolism; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000737:chemistry / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000737:chemistry / Q000378:metabolism*; D008970:Molecular Weight; D029424:Pulmonary Disease, Chronic Obstructive / Q000201:enzymology / Q000276:immunology / Q000662:veterinary*
D004391:Dust; D004731:Endotoxins; D008070:Lipopolysaccharides; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9