| 1. |
- Demoule, Alexandre, et al.
(författare)
-
Relationship between pressure-volume curve and markers for collagen turn-over in early acute respiratory distress syndrome
- 2006
-
Ingår i: Intensive Care Medicine. - : Springer Science and Business Media LLC. - 0342-4642 .- 1432-1238. ; 32:3, s. 413-420
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: In acute respiratory distress syndrome, the relationships between changes in the elastic behavior of the respiratory system and biological markers of extra-cellular matrix or surfactant turn-over could give some insights into its pathophysiological determinants. DESIGN AND MEASUREMENTS: In 17 patients with acute respiratory distress syndrome, we assessed the relationship between chord compliance measured on pressure-volume curves obtained at two levels of positive end-expiratory pressure (0 and 10[Symbol: see text]cm[Symbol: see text]H(2)O) and biological markers of collagen turn-over or surfactant degradation in bronchoalveolar lavage fluid obtained simultaneously in the early phase of the disease (first 4 days). MAIN RESULTS: The compliance of the respiratory system obtained from the pressure-volume curves was significantly correlated with markers for collagen turn-over (type III procollagen peptide and matrix metalloproteinase 2) and with markers of surfactant degradation (type-IIA secretory phospholipase A2). The correlations were stronger when the curve was traced from positive end-expiratory pressure, suggesting that this condition may improve the assessment of tissue mechanics. A logarithmic relationship best described the correlation between compliance and type III procollagen peptide, in agreement with a collagen-dependent model of maximal distension. The marker for surfactant degradation was associated with ongoing alveolar inflammation (cellularity of bronchoalveolar lavage fluid and tumor necrosis factor-alpha concentration). Interleukin-10, an anti-inflammatory mediator, showed no correlation with compliance. CONCLUSION: These preliminary data suggest that a severe reduction in compliance in the early phase of acute respiratory distress syndrome is associated with both collagen deposition and surfactant degradation.
|
|
| 2. |
- Movert, Elin, et al.
(författare)
-
A Novel Bacterial Resistance Mechanism against Human Group IIA-Secreted Phospholipase A2: Role of Streptococcus pyogenes Sortase A.
- 2011
-
Ingår i: Journal of Immunology. - : The American Association of Immunologists. - 1550-6606 .- 0022-1767. ; 187:12, s. 6437-6446
-
Tidskriftsartikel (refereegranskat)abstract
- Human group IIA-secreted phospholipase A(2) (sPLA(2)-IIA) is a bactericidal molecule important for the innate immune defense against Gram-positive bacteria. In this study, we analyzed its role in the host defense against Streptococcus pyogenes, a major human pathogen, and demonstrated that this bacterium has evolved a previously unidentified mechanism to resist killing by sPLA(2)-IIA. Analysis of a set of clinical isolates demonstrated that an ∼500-fold higher concentration of sPLA(2)-IIA was required to kill S. pyogenes compared with strains of the group B Streptococcus, which previously were shown to be sensitive to sPLA(2)-IIA, indicating that S. pyogenes exhibits a high degree of resistance to sPLA(2)-IIA. We found that an S. pyogenes mutant lacking sortase A, a transpeptidase responsible for anchoring LPXTG proteins to the cell wall in Gram-positive bacteria, was significantly more sensitive (∼30-fold) to sPLA(2)-IIA compared with the parental strain, indicating that one or more LPXTG surface proteins protect S. pyogenes against sPLA(2)-IIA. Importantly, using transgenic mice expressing human sPLA(2)-IIA, we showed that the sortase A-mediated sPLA(2)-IIA resistance mechanism in S. pyogenes also occurs in vivo. Moreover, in this mouse model, we also showed that human sPLA(2)-IIA is important for the defense against lethal S. pyogenes infection. Thus, we demonstrated a novel mechanism by which a pathogenic bacterium can evade the bactericidal action of sPLA(2)-IIA and we showed that sPLA(2)-IIA contributes to the host defense against S. pyogenes infection.
|
|
| 3. |
- Movert, Elin, et al.
(författare)
-
Secreted Group IIA Phospholipase A2 Protects Humans Against the Group B Streptococcus: Experimental and Clinical Evidence.
- 2013
-
Ingår i: Journal of Infectious Diseases. - : Oxford University Press (OUP). - 1537-6613 .- 0022-1899. ; 208:12, s. 2025-2035
-
Tidskriftsartikel (refereegranskat)abstract
- Group B streptococcus (GBS) is a leading neonatal pathogen and a growing cause of invasive disease in the elderly, with clinical manifestations such as pneumonia and sepsis. Despite its clinical importance, little is known about innate immunity against GBS in humans. Here, we analyze the role of human group IIA secreted phospholipase A2 (sPLA2-IIA), a bactericidal enzyme induced during acute inflammation, in innate immunity against GBS. We show that clinical GBS isolates are highly sensitive to killing by sPLA2-IIA but not by human antimicrobial peptides. Using transgenic mice that express human sPLA2-IIA, we demonstrate that this enzyme is crucial for host protection against systemic infection and lung challenge by GBS. We found that acute sera from humans diagnosed with invasive GBS disease contain increased levels of sPLA2-IIA compared with normal sera from healthy individuals, indicating that GBS induces an sPLA2-IIA response in blood during human infection. We demonstrate that clinically relevant GBS strains are rapidly killed in these acute sera. We also demonstrate that the bactericidal effect is entirely due to sPLA2-IIA, showing that sPLA2-IIA might represent an important component of humoral innate immunity against GBS. Our data provide experimental and clinical evidence that sPLA2-IIA protects humans against GBS infections.
|
|
