Document Detail

Leukocyte-derived and endogenous matrix metalloproteinases in the lamellae of horses with naturally acquired and experimentally induced laminitis.
MedLine Citation:
PMID:  19101039     Owner:  NLM     Status:  MEDLINE    
RATIONALE: Inflammation and dysregulation of endogenous matrix metalloproteinase (MMP) production are implicated in the development of equine laminitis. In this study, we examine quantitative relationships among levels of leukocyte-derived proMMP-9 and MMP-9, lamellar proMMP-2 and MMP-2, and expression of proMMP-2 processing enzymes, MT1-MMP/PACE4, as steps towards determining whether inflammation and dysregulation of endogenous MMP production are independent or co-dependent processes. ANIMALS: Archived samples of lamellae from horses with naturally acquired laminitis (n = 12), and from horses administered a pro-laminitic gastric bolus of starch gruel were used, the latter horses falling into two groups: (i) responders (CHO-R, n = 7), which developed Obel grade 3-lameness and (ii) non-responders (CHO-NR, n = 4), which did not become lame. METHODS: Lamellar tissue extracts were analyzed by gelatin zymography to determine gelatinase content and by a myeloperoxidase ELISA to quantify relative monocyte/neutrophil content in the tissue. Real-time PCR was employed to measure gene expression of MT1-MMP and PACE4. RESULTS AND CONCLUSIONS: Extracts of lamellae from control horses, CHO-NR and horses with chronic (non-aggravated) laminitis had similarly low levels of pro and processed MMP-9 and MMP-2. In contrast, proMMP-9 was significantly elevated in extracts of lamellae from CHO-R and horses with naturally acquired acute and aggravated chronic laminitis. Lamellar MMP-2 was also increased significantly in the CHO-R and aggravated chronic laminitis groups, although not in the horses with naturally acquired acute laminitis. Concentrations of proMMP-9 correlated directly with myeloperoxidase content in lamellar extracts, suggesting production/induction by inflammatory leukocytes. In contrast, concentrations of proMMP-2 and MMP-2 were unrelated to concentrations of myeloperoxidase or proMMP-9 suggesting that leukocyte infiltration and dysregulation of endogenous MMP-2 are independent processes most likely with distinct inducers. Neither MT1-MMP nor PACE4 gene expression was elevated relative to controls in any group; this is discussed with respect to proMMP-2 processing in disease. In addition, variability in relative concentrations of lamellar MMPs observed among horses with Obel grade 3-lameness is discussed in the context of laminitis risk assessment and disease outcome.
John P Loftus; Philip J Johnson; James K Belknap; Amanda Pettigrew; Samuel J Black
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2008-11-07
Journal Detail:
Title:  Veterinary immunology and immunopathology     Volume:  129     ISSN:  0165-2427     ISO Abbreviation:  Vet. Immunol. Immunopathol.     Publication Date:  2009 Jun 
Date Detail:
Created Date:  2009-04-27     Completed Date:  2009-08-18     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8002006     Medline TA:  Vet Immunol Immunopathol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  221-30     Citation Subset:  IM    
Department of Veterinary and Animal Sciences, University of Massachusetts, Amherst, MA 01003, USA.
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MeSH Terms
Carbohydrates / toxicity
Foot Diseases / chemically induced,  enzymology,  veterinary*
Gene Expression Regulation, Enzymologic / drug effects,  physiology
Hoof and Claw / enzymology*,  pathology
Horse Diseases / chemically induced,  metabolism*
Inflammation / chemically induced,  enzymology,  veterinary
Leukocytes / enzymology*
Matrix Metalloproteinases / genetics,  metabolism*
Reg. No./Substance:
0/Carbohydrates; EC 3.4.24.-/Matrix Metalloproteinases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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