Catalase, myeloperoxidase and hydrogen peroxide in cystic fibrosis

Abstract

aaIn cystic fibrosis (CF), the most common autosomal recessive disorder of white populations, abnormal exocrine gland secretions lead to persisting endobronchial bacterial infections [1]. Consequently, large numbers of polymorphonuclear leukocytes (PMN) are recruited to the infected airways where PMN activation and lysosomal enzyme release occur [2]. In particular PMN-elastase (PMN-Ela) has been implicated in chronic lung destruction [2], the major cause of morbidity and mortality in CF, and, consequently, trials of aerosol therapy with a 1 -proteinase inhibitor (α 1 -PI, synonymous: α 1 -antitrypsin) have been initiated [3].It is not yet certain whether toxic oxygen metabolites produced by stimulated PMN also contribute to lung injury in CF, as has been suggested in other airway diseases [4][5][6][7]. However, indirect evidence may support this hypothesis; high sputum concentrations of extracellular myeloperoxidase (MPO), a PMN-derived enzyme which transforms hydrogen peroxide (H 2 O 2 ) into highly reactive oxygen metabolites, have been detected in CF patients [8][9][10][11], and lung function has been inversely correlated with MPO levels [9][10][11]. In addition, increased lipid peroxidation [12], reduced free-radical-trapping capacity [13] and altered plasma antioxidant status [12][13][14] have been reported to occur in CF patients.In this study, we have attempted to test this hypothesis by measuring H 2 O 2 concentrations in breath condensates of CF patients, to determine in CF sputum samples activities and concentrations of MPO and catalase (CAT), an enzyme that detoxifies H 2 O 2 to oxygen and water, and, also, to investigate a possible cytotoxic effect of CF sputum on cells and on α 1 -PI in vitro. Materials and methods PatientsA total of 63 CF patients from six German CF clinics were studied. Patients (mean±SD (range) age 24±8 (8-37) yrs, males n=30; females n=33) had significantly increased sweat electrolyte levels [15], and were chronically infected by Pseudomonas aeruginosa (n=30) or other pathogens (n=33). All patients were receiving pancreatic enzyme replacement therapy, but no anti-inflammatory medication. All hospitalized patients (n=23) were being treated with parenteral antibiotics against P. aeruginosa. Of the hospitalized patients 10 suffered from acute exacerbations. Mean±SD maximal vital capacity (VCmax) (75±19%) and forced expiratory volume in one second (FEV1) (69±25%) in the CF patients ranked below normal age-predicted values. A total of 54% of the patients had moderately reduced lung function and 46% had severely reduced lung function. Controls included 51 healthy, nonsmoking subjects (27±8 (12-61) yrs) and 23 patients with bronchial asthma (36±16 (12-61) In conclusion, catalase, sulphated glycoconjugates and deoxyribonucleic acid may prevent myeolperoxidase-mediated oxygen radical generation in cystic fibrosis sputum.

Hydrogen peroxide and nitric oxide in exhaled air of children with cystic fibrosis during antibiotic treatment

“…In this study in CF-children with acute infective pulmonary exacerbations higher levels were found than in healthy children [21], and a significant decrease of serial exhaled H 2 O 2 levels in the course of treatment with antibiotics was also found. The observed H 2 O 2 concentrations at the end of the treatment period are similar to those found previously in healthy children [21], and are in agreement with the results of stable CF-adults [22,29]. Thus, exhaled H 2 O 2 may not be a suitable marker of airway inflammation in stable CFpatients, but is of potential value to monitor the effect of anti-inflammatory treatment for exerbations.…”

“…Hence, markers of inflammation like H 2 O 2 and NO that can be obtained easily and repeatedly are potentially important for monitoring CF lung disease. Exhaled H 2 O 2 levels in adult CF-patients were investigated earlier and appeared not to be significantly different from those of healthy controls [22,29]. In this study in CF-children with acute infective pulmonary exacerbations higher levels were found than in healthy children [21], and a significant decrease of serial exhaled H 2 O 2 levels in the course of treatment with antibiotics was also found.…”

“…That exhaled H 2 O 2 is not elevated in stable CF-patients is possibly due to an increase of scavenging by for example glutathione or catalase which may balance the increased oxidative stress [29]. In that case, the results suggest that infective pulmonary exacerbations may disturb such a balance, and this could be due to various mechanisms.…”

The antioxidant role of thiocyanate in the pathogenesis of cystic fibrosis and other inflammation-related diseases

“…A massive number of neutrophils and macrophages are attracted to infection sites, releasing MPO and H 2 O 2 (30) along with other bactericidal and inflammatory agents. MPO activity is known to inflict severe injuries on airway epithelial cells (20), as well as to stop ciliary beating (H 2 O 2 is also known to inhibit ciliary beating) (39,40). Cilia normally propel pathogens out of the airways, and their impairment would allow bacteria to remain and develop infection (41,42).…”

Breath Analysis: Potential for Clinical Diagnosis and Exposure Assessment

“…Recently, Montuschi (54 ) reviewed EBC analyses in patients with COPD and listed related breath markers, including H 2 O 2 , eicosanoids (leukotrienes, prostanoids, and isoprostanes), NO-derived products (S-nitrosothiols, nitrite, and nitrate), pH, aldehydes, and others. Moreover, CO has also been studied as a breath marker of asthma (55)(56)(57) and CF (58,59 ); H 2 O 2 as a breath marker of asthma (60,61 ), COPD (62,63 ), and CF (64,65 ); isoprostanes as breath markers of asthma (66 ), COPD (67 ), and CF (68 ); and nitrite/nitrate as breath markers of asthma (69 ) and CF (70,71 ).…”