Surfactant proteins B and C are both necessary for alveolar stability at end expiration in premature rabbits with respiratory distress syndrome

2008 ◽  
Vol 104 (4) ◽  
pp. 1101-1108 ◽  
Author(s):  
Andreas Almlén ◽  
Guido Stichtenoth ◽  
Bim Linderholm ◽  
Marie Haegerstrand-Björkman ◽  
Bengt Robertson ◽  
...  
Keyword(s):  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Distress Syndrome ◽  
Surfactant Protein ◽  
Synthetic Surfactant ◽  
Positive End Expiratory Pressure ◽  
Natural Surfactant ◽  
Alveolar Stability ◽  
The Individual ◽  
Artificial Surfactant

Modified natural surfactant preparations, used for treatment of respiratory distress syndrome in premature infants, contain phospholipids and the hydrophobic surfactant protein (SP)-B and SP-C. Herein, the individual and combined effects of SP-B and SP-C were evaluated in premature rabbit fetuses treated with airway instillation of surfactant and ventilated without positive end-expiratory pressure. Artificial surfactant preparations composed of synthetic phospholipids mixed with either 2% (wt/wt) of porcine SP-B, SP-C, or a synthetic poly-Leu analog of SP-C (SP-C33) did not stabilize the alveoli at the end of expiration, as measured by low lung gas volumes of ∼5 ml/kg after 30 min of ventilation. However, treatment with phospholipids containing both SP-B and SP-C/SP-C33 approximately doubled lung gas volumes. Doubling the SP-C33 content did not affect lung gas volumes. The tidal volumes were similar in all groups receiving surfactant. This shows that SP-B and SP-C exert different physiological effects, since both proteins are needed to establish alveolar stability at end expiration in this animal model of respiratory distress syndrome, and that an optimal synthetic surfactant probably requires the presence of mimics of both SP-B and SP-C.

scholarly journals Annexin A2 Mediates Mycoplasma pneumoniae Community-Acquired Respiratory Distress Syndrome Toxin Binding to Eukaryotic Cells

mBio ◽  
2014 ◽  
Vol 5 (4) ◽  
Author(s):  
Sudha R. Somarajan ◽  
Fadi Al-Asadi ◽  
Kumaraguruparan Ramasamy ◽  
Lavanya Pandranki ◽  
Joel B. Baseman ◽  
...  
Keyword(s):  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Mammalian Cells ◽  
Distress Syndrome ◽  
Protein A ◽  
A549 Cells ◽  
Surfactant Protein ◽  
Annexin A2 ◽  
Toxin Binding ◽  
Cards Toxin

ABSTRACT Mycoplasma pneumoniae synthesizes a novel human surfactant protein A (SP-A)-binding cytotoxin, designated community-acquired respiratory distress syndrome (CARDS) toxin, that exhibits ADP-ribosylating and vacuolating activities in mammalian cells and is directly linked to a range of acute and chronic airway diseases, including asthma. In our attempt to detect additional CARDS toxin-binding proteins, we subjected the membrane fraction of human A549 airway cells to affinity chromatography using recombinant CARDS toxin as bait. A 36-kDa A549 cell membrane protein bound to CARDS toxin and was identified by time of flight (TOF) mass spectroscopy as annexin A2 (AnxA2) and verified by immunoblotting with anti-AnxA2 monoclonal antibody. Dose-dependent binding of CARDS toxin to recombinant AnxA2 reinforced the specificity of the interaction, and further studies revealed that the carboxy terminus of CARDS toxin mediated binding to AnxA2. In addition, pretreatment of viable A549 cells with anti-AnxA2 monoclonal antibody or AnxA2 small interfering RNA (siRNA) reduced toxin binding and internalization. Immunofluorescence analysis of CARDS toxin-treated A549 cells demonstrated the colocalization of CARDS toxin with cell surface-associated AnxA2 upon initial binding and with intracellular AnxA2 following toxin internalization. HepG2 cells, which express low levels of AnxA2, were transfected with a plasmid expressing AnxA2 protein, resulting in enhanced binding of CARDS toxin and increased vacuolization. In addition, NCI-H441 cells, which express both AnxA2 and SP-A, upon AnxA2 siRNA transfection, showed decreased binding and subsequent vacuolization. These results indicate that CARDS toxin recognizes AnxA2 as a functional receptor, leading to CARDS toxin-induced changes in mammalian cells. IMPORTANCE Host cell susceptibility to bacterial toxins is usually determined by the presence and abundance of appropriate receptors, which provides a molecular basis for toxin target cell specificities. To perform its ADP-ribosylating and vacuolating activities, community-acquired respiratory distress syndrome (CARDS) toxin must bind to host cell surfaces via receptor-mediated events in order to be internalized and trafficked effectively. Earlier, we reported the binding of CARDS toxin to surfactant protein A (SP-A), and here we show how CARDS toxin uses an alternative receptor to execute its pathogenic properties. CARDS toxin binds selectively to annexin A2 (AnxA2), which exists both on the cell surface and intracellularly. Since AnxA2 regulates membrane dynamics at early stages of endocytosis and trafficking, it serves as a distinct receptor for CARDS toxin binding and internalization and enhances CARDS toxin-induced vacuolization in mammalian cells.

Lung volumes and alveolar expansion pattern in immature rabbits treated with serum-diluted surfactant

2004 ◽  
Vol 97 (4) ◽  
pp. 1408-1413 ◽  
Author(s):  
Yongmei Xu ◽  
Tsutomu Kobayashi ◽  
Xiaoguang Cui ◽  
Keisuke Ohta ◽  
Chiharu Kabata ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Distress Syndrome ◽  
Ringer Solution ◽  
Natural Surfactant ◽  
Volume Curve ◽  
Pressure Volume Curve ◽  
Expansion Pattern

In acute respiratory distress syndrome, mechanical ventilation often induces alveolar overdistension aggravating the primary insult. To examine the mechanism of overdistension, surfactant-deficient immature rabbits were anesthetized with pentobarbital sodium, and their lungs were treated with serum-diluted modified natural surfactant (porcine lung extract; 2 mg/ml, 10 ml/kg). By mechanical ventilation with a peak inspiration pressure of 22.5 cmH2O, the animals had a tidal volume of 14.7 ml/kg (mean), when 2.5 cmH2O positive end-expiratory pressure was added. This volume was similar to that in animals treated with nondiluted modified natural surfactant (24 mg/ml in Ringer solution, 10 ml/kg). However, the lungs fixed at 10 cmH2O on the deflation limbs of the pressure-volume curve had the largest alveolar/alveolar duct profiles (≥48,000 μm2), accounting for 38% of the terminal air spaces, and the smallest (<6,000 μm2), accounting for 31%. These values were higher than those in animals treated with nondiluted modified natural surfactant ( P < 0.05). We conclude that administration of serum-diluted surfactant to immature neonatal lungs leads to patchy overdistension of terminal air spaces, similar to the expansion pattern that may be seen after dilution of endogenous surfactant with proteinaceous edema fluid in acute respiratory distress syndrome.

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