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. 2012 Dec 11;13(1):113.
doi: 10.1186/1465-9921-13-113.

Specific IgA and metalloproteinase activity in bronchial secretions from stable chronic obstructive pulmonary disease patients colonized by Haemophilus influenzae

Laura Millares  1 , Alicia Marin, Judith Garcia-Aymerich, Jaume Sauleda, José Belda, Eduard Monsó; PAC-COPD Study Group
Collaborators, Affiliations

Specific IgA and metalloproteinase activity in bronchial secretions from stable chronic obstructive pulmonary disease patients colonized by Haemophilus influenzae

Laura Millares et al. Respir Res. .

Abstract

Background: Haemophilus influenzae is the most common colonizing bacteria of the bronchial tree in chronic obstructive pulmonary disease (COPD), and positive cultures for this potentially pathogenic microorganism (PPM) has been associated with local inflammation changes that may influence the relationships between H. influenzae and the bronchial mucosa.

Methods: A cross-sectional analysis of stable COPD patients enrolled in the Phenotype and Course of Chronic Obstructive Pulmonary Disease (PAC-COPD) Study, focusing on bronchial colonization by H. influenzae, was performed. Specific IgA against the PPM was measured by optical density, and metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) using ELISA in sputum samples. Levels in patients colonized by H. influenzae and non-colonized patients were compared.

Results: Sputum supernatant for the measurement of specific IgA against H. influenzae was available from 54 stable COPD patients, who showed levels of specific IgA significantly lower in colonized (n=21) than in non-colonized patients (n=33) (15 [4-37] versus 31 [10-75], p=0.033, Mann-Whitney U test). Proenzyme MMP-9 was measured in 44 patients, and it was higher in colonized (n=12, 1903 [1488-6699] ng/ml) than in non-colonized patients (n=32, 639 [373-972] ng/ml) (p<0.001, Mann-Whitney U test). Active form of MMP-9 was also higher in colonized (126 [25-277] ng/ml) than in non-colonized patients (39 [14-68] ng/ml) (p=0.021, Mann-Whitney U test), and the molar ratio between proenzyme MMP-9 and TIMP-1 was above 1 (2.1 [0.1-12.5]) in colonized patients, significantly higher than the ratio found in non-colonized patients (0.2 [0.08-0.5]) (p=0.030, Mann-Whitney U test).

Conclusions: Clinically stable COPD patients colonized by H. influenzae had lower levels of specific IgA against the microorganism and higher values of the active form of MMP-9 in their sputum supernatant than non-colonized patients. Bronchial colonization by H. influenzae may cause structural changes in the extracellular matrix through a defective defense and the production of active metalloproteinases.

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Figures

Figure 1
Figure 1
Ten distinct isolates of H. Influenzae, isolated from COPD patients, used as capture antigen in ELISA testing.
Figure 2
Figure 2
Flow chart showing the number of subjects used in each analysis.
Figure 3
Figure 3
Level of specific IgA against H. influenzae in patients colonized by this bacteria (n=21) and non-colonized patients (n=33). Results expressed as optical density (OD) ratio between patients and healthy controls.
Figure 4
Figure 4
Proenzyme MMP-9 concentration in the sputum supernatant of patients colonized by H. influenzae (n=12) and non-colonized patients (n=32).
Figure 5
Figure 5
TIMP-1 concentration in the sputum supernatant of patients colonized by H. influenzae (n=12) and non-colonized patients (n=32).
Figure 6
Figure 6
Active MMP-9 concentration in the sputum supernatant of patients colonized by H. influenzae (n=12) and non- colonized patients (n=32).
Figure 7
Figure 7
Molar ratio between proenzyme MMP-9 and TIMP-1 in colonized patients colonized by H. influenzae (n=12) and non-colonized patients (n=32).
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References

    1. Sethi S, Murphy TF. Infection in the pathogenesis and course of chronic obstructive pulmonary disease. N Engl J Med. 2008;359(22):2355–2365. doi: 10.1056/NEJMra0800353. - DOI - PubMed
    1. Berenson CS, Murphy TF, Wrona CT, Sethi S. Outer membrane protein P6 of nontypeable Haemophilus influenzae is a potent and selective inducer of human macrophage proinflammatory cytokines. Infect Immun. 2005;73(5):2728–2735. doi: 10.1128/IAI.73.5.2728-2735.2005. - DOI - PMC - PubMed
    1. Doring G, Parameswaran IG, Murphy TF. Differential adaptation of microbial pathogens to airways of patients with cystic fibrosis and chronic obstructive pulmonary disease. FEMS Microbiol Rev. pp. 124–146. - PubMed
    1. Srikhanta YN, Fox KL, Jennings MP. The phasevarion: phase variation of type III DNA methyltransferases controls coordinated switching in multiple genes. Nat Rev Microbiol. 2010;8(3):196–206. doi: 10.1038/nrmicro2283. - DOI - PubMed
    1. Starner TD, Zhang N, Kim G, Apicella MA, McCray PB Jr. Haemophilus influenzae forms biofilms on airway epithelia: implications in cystic fibrosis. Am J Respir Crit Care Med. 2006;174(2):213–220. doi: 10.1164/rccm.200509-1459OC. - DOI - PMC - PubMed

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