Matrix metalloproteases in bronchoalveolar lavage fluid of patients with type III Pseudomonas aeruginosa pneumonia - 07/08/11
, Daniel Amsterdam c, Ahmad Alhajhusain a, b, Morohonfolu E. Akinnusi a, Ranime G. Saliba a, Susan V. Lynch d, Jeanine P. Wiener-Kronish e
Corresponding author. Veterans Affairs Western New York Healthcare System, Medical Research Building 20, 3495 Bailey Avenue, Buffalo, NY 14215-1199, USA. Tel.: +1 716 862 7366; fax: +1 716 862 8632.Summary |
Objectives |
In patients with ventilator-associated pneumonia (VAP), Pseudomonas aeruginosa type III (TTSS) secreting isolates have been linked to poor clinical outcomes. Differential expression of matrix metalloproteinases (MMPs) induced by type III effector proteins may herald an irreversible lung injury.
Methods |
Serial bronchoalveolar lavage fluids collected from 41 patients with P. aeruginosa at onset of VAP, day 4, and day 8 after antibiotic therapy were assayed for MMP-8, MMP-9, tissue inhibitor of metalloproteinase-1 (TIMP-1), and ⍺-2 macroglobulin levels.
Results |
At the onset of VAP, isolates secreting ExoU had the highest MMP-9 levels. The response to antimicrobial therapy showed a differential drop in MMPs with significant decrease in MMP-8 and MMP-9 levels on days 4 and 8 in patients with TTSS− compared to TTSS+ phenotype. The ratio of MMP-9/TIMP-1 was significantly associated with ⍺-2 macroglobulin at end of therapy (r=0.4, p=0.02). Patients who survived had a lower MMP-9/TIMP-1 ratio than those who died (p=0.003).
Conclusions |
VAP linked to P. aeruginosa Type III phenotype portrays a divergent antibiotic treatment response in regards to the concentrations of metalloproteinases in the alveolar space. The imbalance between MMP-9 and TIMP-1 may determine the intensity of alveolocapillary damage and ultimate outcome of P. aeruginosa VAP.
Le texte complet de cet article est disponible en PDF.Keywords : Pseudomonas aeruginosa, Exotoxin, Metalloproteinases, Ventilator-associated pneumonia
Plan
Vol 59 - N° 1
P. 49-55 - juillet 2009 Retour au numéro
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