Hospital acquired pneumonia with high-risk bacteria is associated with increased pulmonary matrix metalloproteinase activity.
BACKGROUND
Neutrophil products like matrix metalloproteinases (MMP), involved in bacterial defence mechanisms, possibly induce lung damage and are elevated locally during hospital- acquired pneumonia (HAP). In HAP the virulence of bacterial species is known to be different. The aim of this study was to investigate the influence of high-risk bacteria like S. aureus and pseudomonas species on pulmonary MMP concentration in human pneumonia.


METHODS
In 37 patients with HAP and 16 controls, MMP-8, MMP-9 and tissue inhibitors of MMP (TIMP) were analysed by ELISA and MMP-9 activity using zymography in bronchoalveolar lavage (BAL).


RESULTS
MMP-9 activity in mini-BAL was increased in HAP patients versus controls (149 +/- 41 vs. 34 +/- 11, p < 0.0001). In subgroup analysis, the highest MMP concentrations and activity were seen in patients with high-risk bacteria: patients with high-risk bacteria MMP-9 1168 +/- 266 vs. patients with low-risk bacteria 224 +/- 119 ng/ml p < 0.0001, MMP-9 gelatinolytic activity 325 +/- 106 vs. 67 +/- 14, p < 0.0002. In addition, the MMP-8 and MMP-9 concentration was associated with the state of ventilation and systemic inflammatory marker like CRP.


CONCLUSIONS
Pulmonary MMP concentrations and MMP activity are elevated in patients with HAP. This effect is most pronounced in patients with high-risk bacteria. Artificial ventilation may play an additional role in protease activation.
Schaaf
Bernhard
B
Medical Clinic III, University of Lübeck, Lübeck, Germany. schaaf@uni-luebeck.de
Liebau
Cornelia
C
Kurowski
Volkhard
V
Droemann
Daniel
D
Dalhoff
Klaus
K
D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D003428:Cross Infection / Q000201:enzymology* / Q000382:microbiology / Q000503:physiopathology / Q000628:therapy; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D016905:Gram-Negative Bacterial Infections / Q000201:enzymology; D006801:Humans; D008168:Lung / Q000201:enzymology* / Q000378:metabolism; D008297:Male; D020784:Matrix Metalloproteinase 8 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D008875:Middle Aged; D009994:Osmolar Concentration; D018410:Pneumonia, Bacterial / Q000201:enzymology* / Q000382:microbiology / Q000503:physiopathology / Q000628:therapy; D011552:Pseudomonas Infections / Q000201:enzymology; D012119:Respiration; D012121:Respiration, Artificial; D013203:Staphylococcal Infections / Q000201:enzymology; D020615:Stenotrophomonas maltophilia; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D015854:Up-Regulation
D019715:Tissue Inhibitor of Metalloproteinase-1; D020784:Matrix Metalloproteinase 8; D020780:Matrix Metalloproteinase 9