These small vesicles are generated after inspiration/expiration cycles (19)

These small vesicles are generated after inspiration/expiration cycles (19). In this study, we used two types of lipid vesicles with different sizes, composed of either the hydrophobic fraction of surfactant (PL/SP-B/SP-C) or a mixture of surfactant lipids (DPPC/POPG/PA). unilamellar vesicles (SUVs, 0.1 m diameter), which are generated after inspiration/expiration cycles, and are endocytosed by pneumocytes for his or her degradation and/or recycling. Results indicated that extracellular pulmonary surfactant binds to NTHi, avoiding NTHi self-aggregation and inhibiting adhesion of NTHi to pneumocytes and, as a result, inhibiting NTHi invasion. In contrast, endocytosed surfactant lipids, primarily via the scavenger receptor SR-BI, did not affect NTHi adhesion but inhibited NTHi invasion by obstructing bacterial uptake in pneumocytes. This blockade was made possible by inhibiting Akt phosphorylation and Rac1 GTPase activation, which are signaling pathways involved in NTHi internalization. Administration of the hydrophobic portion of lung surfactant accelerated bacterial clearance inside a mouse model of NTHi pulmonary illness, supporting the notion the lipid component of lung surfactant protects against NTHi illness. These results suggest that alterations in surfactant lipid levels in COPD individuals may increase susceptibility to illness by this pathogen. (NTHi) is definitely a non-capsulated Gram-negative bacterium that has been recognized as a major causative pathogen of mucosal infections such as otitis press in children and exacerbations of chronic obstructive pulmonary disease (COPD) in adults (1C5). NTHi is definitely a common commensal of the human being nasopharynx that induces a polymicrobial disease, typically due to concurrent or predisposing respiratory viral illness (3). In the top respiratory tract, the main pathological condition caused by NTHi is acute otitis press, with almost 60% of the cases attributable to this bacterium (1). In the lower airways, NTHi infections are highly common in individuals suffering from COPD, bronchiectasis, cystic fibrosis, and pneumonia (1, 2). In particular, NTHi is a very Rabbit Polyclonal to ELAV2/4 common bacterial colonizer in the airways of COPD individuals, and is the most frequently isolated bacterium in exacerbations of COPD, contributing to swelling and disease progression (2, 5). One of the mechanisms likely to be involved in the persistence of respiratory infections by NTHi is definitely its capacity to invade airway epithelial cells (2, 5C7). Intracellular NTHi has been recognized in epithelial cells from bronchial biopsies of individuals suffering chronic bronchitis (8) and COPD (9). Intracellular invasion of lung epithelial cells enables NTHi to escape from the sponsor immune system and to reside Z-360 calcium salt (Nastorazepide calcium salt) inside cells with high access to essential nutrients (10). Moreover, intracellular NTHi is definitely safeguarded from high concentrations of antibiotics, hampering medical treatment (11). Consequently, we put forward the notion that avoiding NTHi from invading lung epithelial cells is definitely crucially important for the prophylaxis and treatment of respiratory NTHi infections. To penetrate into airway epithelial cells, adherence of NTHi to such cells is essential, and several adhesion molecules on NTHi have been identified (12C15). They can bind either integrin receptors within the epithelial cell surface (6) or extracellular matrix proteins that interact with the epithelium (13, 15). In healthy individuals, the alveolar epithelium is definitely remarkably well-defended from bacterial infection through multiple mechanisms of bacterial clearance, including manifestation of antimicrobial peptides, lung collectins (SP-A and SP-D), and active Z-360 calcium salt (Nastorazepide calcium salt) monitoring of airway macrophages (16C18). In this study, we wondered whether the complicated network of extracellular membranes, called pulmonary surfactant, could also protect the sponsor from NTHi adhesion and invasion. Pulmonary surfactant is definitely a complex lipoprotein system, exquisitely conserved across species. Surfactant is composed of 90 wt % lipids and 10 wt % proteins. Phospholipids are the major lipid component of surfactant, especially dipalmitoylphosphatidylcholine (DPPC) (19, 20). Phosphatidylglycerol (PG) represents a major unsaturated anionic component (19, 20). Four surfactant proteins form part of this material: the hydrophobic proteins SP-B and SP-C, which are put in surfactant membranes and are essential for surfactant biophysical function, and the soluble collectins SP-A and SP-D, which are involved in innate immune sponsor defense (18C24). Lung surfactant Z-360 calcium salt (Nastorazepide calcium salt) is definitely synthesized and secreted by type II pneumocytes. After secretion to the alveolar space, SP-B/SP-C and phospholipids form a multilayered surface film in the air-liquid interface that decreases alveolar surface pressure on expiration, and thus prevents lung collapse and respiratory failure (19, 20). Airway instillation of surfactant is definitely in general use for treatment of respiratory stress syndrome in preterm babies (25, 26). Alternative surfactants consist of lipid extract preparations.

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