Excessive matrix metalloproteinase-9 in the plasma of community-acquired pneumonia
Introduction
Pneumonia is an inflammation of the lung caused by infection with bacteria, viruses or other organisms [1]. Pneumonia is often classified into two categories including community-acquired pneumonia (CAP) and hospital-acquired pneumonia (HAP) that may help predicting the organisms that are the most likely causes [2]. CAP, still an important cause of mortality in spite of effective antibiotics [3], [4], affects nearly 4 million adults each year and Streptococcus pneumoniae is the most common pneumonia-causing bacteria, while other organisms, such as atypical bacteria called Chlamydia or Mycoplasma pneumonia, are also common causes of CAP [5].
In the processing of bacterial CAP, blood leukocytes respond to bacteria or bacterial products by secreting various substances, such as proinflammatory cytokines, chemokines, enzymes, oxygen and nitrogen radicals [4], [6]. Among the enzymes secreted by leukocytes, matrix metalloproteinases (MMPs) play an important role in the pathogenesis of several inflammatory diseases [7], [8]. MMPs are a large family of zinc and calcium-dependent endopeptidases with different substrate specificities, cellular sources and inducibility [8], [9]. These enzymes are secreted as inactive proenzymes (or zymogens) and are autoactivated or activated by other proteolytic enzymes on site, resulting in the degradation of extracellular matrix. MMPs play an important role in physiological and pathological processes, including tumor migration, tissue remodeling and cell inflammation [10], [11]. Of the MMP family, MMP-9 appears to be important for the migration of polymorphonuclear neutrophils (PMNs) across basement membranes [12], [13].
Recently, various studies have shown that MMPs are implicated in the pathogenesis of various pulmonary inflammatory diseases like various pulmonary inflammatory diseases such as acute respiratory distress syndrome [14], bronchiectasis [15], cystic fibrosis [16], interstitial lung disease [17], chronic obstructive pulmonary disease [18] and hospital-acquired pneumonia [19]. Nevertheless, previous studies were focused on only bronchalveolar lavage (BAL) fluid or sputum in various pulmonary inflammatory diseases. However, the MMP-9 activity and MMP-9 level in the plasma of community-acquired pneumonia have not yet been studied. In the present study, MMP-9 activity and MMP-9 level in the plasma of CAP patients and whether MMP-9 activity and MMP-9 level were related to the effectiveness of an antibiotics treatment was determined. Since PMNs are the main source of MMP-9 in the presence of pneumonia, the correlation between MMP-9 level and peripheral PMNs was also investigated.
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Subjects and specimen collection
Venous blood samples were obtained via routine venipuncture from CAP patients of the Armed-Force Taichung General Hospital, Taichung, Taiwan. A total of 81 subjects, including 35 control subjects and 46 CAP patients, were recruited into this study. Pneumonia was diagnosed on the basis of a lung radiographic opacity and at least two of the following conditions: fever (>38.5 °C), purulent expectoration, pleuritic chest pain or leukocytosis (white blood cell count of >10,000/mm3). Based the CAP
Characteristics and blood cell counts of subjects
The clinical characteristics of the normal subjects (including 20 men and 15 women, age 42.2±3.4 years) and CAP patients (including 28 men and 18 women, age 48±3.6 years) are summarized in Table 1. The total WBC counts of CAP patients were significantly higher than in controls (P<0.001). Furthermore, the total WBC counts and the percentages of neutrophils of CAP patients were significantly reduced after treated with antibiotics (P<0.001 and P<0.001, respectively) (Table 1, Fig. 1A and B), while
Discussion
CAP had ever been an important cause of mortality until the emergence of effective antibiotics. Among possible etiological factors, bacteria have been the most common causes of CAP, while bacterial infection may weaken the patient's defense system together with various accompanied symptoms, such as fever (>38.5 °C), purulent expectoration, pleuritic chest pain or leukocytosis (WBC count of >10,000/mm3). As showed in Fig. 1A, the WBC counts of CAP patients were well over 10,000/mm3, which was
Acknowledgment
This study was supported by grants of National Science Council, Republic of China (NSC93-2320-B-040-061 and NSC93-2313-B-166-001).
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