Hospital acquired pneumonia with high-risk bacteria is associated with increased pulmonary matrix metalloproteinase activity

BMC Pulm Med. 2008 Aug 12;8:12. doi: 10.1186/1471-2466-8-12.

Abstract

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.

Conclusion: 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.

MeSH terms

  • Bronchoalveolar Lavage Fluid / chemistry
  • Cross Infection / enzymology*
  • Cross Infection / microbiology
  • Cross Infection / physiopathology
  • Cross Infection / therapy
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Gram-Negative Bacterial Infections / enzymology
  • Humans
  • Lung / enzymology*
  • Lung / metabolism
  • Male
  • Matrix Metalloproteinase 8 / metabolism*
  • Matrix Metalloproteinase 9 / metabolism*
  • Middle Aged
  • Osmolar Concentration
  • Pneumonia, Bacterial / enzymology*
  • Pneumonia, Bacterial / microbiology
  • Pneumonia, Bacterial / physiopathology
  • Pneumonia, Bacterial / therapy
  • Pseudomonas Infections / enzymology
  • Respiration
  • Respiration, Artificial
  • Staphylococcal Infections / enzymology
  • Stenotrophomonas maltophilia
  • Tissue Inhibitor of Metalloproteinase-1 / metabolism
  • Up-Regulation

Substances

  • Tissue Inhibitor of Metalloproteinase-1
  • Matrix Metalloproteinase 8
  • Matrix Metalloproteinase 9