Matrix metalloproteases in bronchoalveolar lavage fluid of patients with type III Pseudomonas aeruginosa pneumonia.
OBJECTIVE
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 alpha-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 alpha-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.
El-Solh
Ali A
AA
The Veterans Affairs Western New York Healthcare System, Medical Research Building 20, 3495 Bailey Avenue, Buffalo, NY 14215-1199, USA. solh@buffalo.edu
Amsterdam
Daniel
D
Alhajhusain
Ahmad
A
Akinnusi
Morohonfolu E
ME
Saliba
Ranime G
RG
Lynch
Susan V
SV
Wiener-Kronish
Jeanine P
JP
D000368:Aged; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry*; D005260:Female; D006801:Humans; D008297:Male; D020784:Matrix Metalloproteinase 8 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D008875:Middle Aged; D018410:Pneumonia, Bacterial / Q000201:enzymology* / Q000453:epidemiology; D053717:Pneumonia, Ventilator-Associated / Q000453:epidemiology; D011552:Pseudomonas Infections / Q000201:enzymology*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism
D019715:Tissue Inhibitor of Metalloproteinase-1; D020782:Matrix Metalloproteinases; D020784:Matrix Metalloproteinase 8; D020780:Matrix Metalloproteinase 9