This Article Full Text Full Text (PDF) Online Supplement Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hartog, C. M. Articles by Braun, J. Search for Related Content PubMed PubMed Citation Articles by Hartog, C. M. Articles by Braun, J.

Pulmonary Matrix Metalloproteinase Excess in Hospital-acquired Pneumonia

Medizinische Klinik III and Klinik für Anaesthesiologie, Medical University of Lübeck, Lübeck, Germany

Correspondence and requests for reprints should be addressed to Joerg Braun, 1, Medizinische Abteilung des AK Wandsbek, Alphonsstraße 14, 22043 Hamburg, Germany. E-mail: joerg.braun{at}ak-wandsbek.lbk-hh.de

In hospital-acquired pneumonia, extracellular matrix destruction is common and may be caused by excessive activity of matrix metalloproteinases (MMPs). Thirty patients with hospital-acquired pneumonia and 16 control subjects were studied. We evaluated the concentrations of MMP-8, MMP-9, and tissue inhibitor of metalloproteinase-1 in mini-bronchoalveolar lavage fluid (mini-BALF) and blood using zymography and specific immunoassays. In patients with hospital-acquired pneumonia concentrations of MMP-8 and MMP-9 in mini-BALF were increased 10-fold, whereas their specific inhibitor tissue inhibitor of metalloproteinase-1 was not concomitantly increased. In 80% of patients with pneumonia, but in none of the control subjects, the active form of MMP-9 was detected by zymography. Zymography furthermore showed the banding pattern of neutrophil-derived MMP-9, indicating that neutrophils were the main source of MMP-9. Comparison of neutrophils from blood and mini-BALF showed higher basal release of MMPs by pulmonary neutrophils. Stimulation analysis indicated that pulmonary neutrophils were already maximally activated. In patients with detection of potentially pathogenic microorganisms, concentrations of MMPs were fivefold increased compared with patients with negative cultures. Furthermore, MMP-levels were related to clinical severity. These are the first data suggesting that neutrophil-derived MMPs are increased in hospital-acquired pneumonia in association to the detection of causative microorganisms and clinical severity.

Key Words: matrix metalloproteinases • TIMP-1 hospital-acquired pneumonia • polymorphonuclear neutrophils

This article has been cited by other articles:

				R. Cockeran, T. J. Mitchell, C. Feldman, and R. Anderson Pneumolysin induces release of matrix metalloproteinase-8 and -9 from human neutrophils Eur. Respir. J., November 1, 2009; 34(5): 1167 - 1170. [Abstract] [Full Text] [PDF]

				C. L. Ventura, R. Higdon, L. Hohmann, D. Martin, E. Kolker, H. D. Liggitt, S. J. Skerrett, and C. E. Rubens Staphylococcus aureus Elicits Marked Alterations in the Airway Proteome during Early Pneumonia Infect. Immun., December 1, 2008; 76(12): 5862 - 5872. [Abstract] [Full Text] [PDF]

				P T G Elkington and J S Friedland Matrix metalloproteinases in destructive pulmonary pathology Thorax, March 1, 2006; 61(3): 259 - 266. [Abstract] [Full Text] [PDF]

				R. H. Hubner, S. Meffert, U. Mundt, H. Bottcher, S. Freitag, N. E. El Mokhtari, T. Pufe, S. Hirt, U. R. Folsch, and B. Bewig Matrix metalloproteinase-9 in bronchiolitis obliterans syndrome after lung transplantation Eur. Respir. J., March 1, 2005; 25(3): 494 - 501. [Abstract] [Full Text] [PDF]

				M. J. Tobin Critical Care Medicine in AJRCCM 2003 Am. J. Respir. Crit. Care Med., January 15, 2004; 169(2): 239 - 253. [Full Text] [PDF]

				M. J. Tobin Tuberculosis, Lung Infections, Interstitial Lung Disease, Social Issues and Journalology in AJRCCM 2003 Am. J. Respir. Crit. Care Med., January 15, 2004; 169(2): 288 - 300. [Full Text] [PDF]

				E. C. Gabazza, O. Taguchi, and Y. Adachi Do Matrix Metalloproteinases Protect or Worsen Pneumonia? Am. J. Respir. Crit. Care Med., January 1, 2004; 169(1): 133 - 133. [Full Text]