Poloxamer 188 Facilitates the Repair of Alveolus Resident Cells in Ventilator-injured Lungs

• Published in: American journal of respiratory and critical care medicine 2011-10, Vol.184 (8), p.939-947
• Main Authors: PLATAKI, Maria, LEE, Yang D, RASMUSSEN, Deborah L, HUBMAYR, Rolf D
• Format: Article
• Language: English
• Subjects: Alveolar Epithelial Cells - drug effects; Alveolar Epithelial Cells - pathology; Alveolar Epithelial Cells - ultrastructure; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; Apoptosis; Biological and medical sciences; Blood. Blood and plasma substitutes. Blood products. Blood cells. Blood typing. Plasmapheresis. Apheresis; Bronchoalveolar Lavage Fluid - chemistry; Cell Membrane - drug effects; Cells; Cytokines; Female; In Vitro Techniques; Inspiratory Capacity; Intensive care medicine; Lung - drug effects; Lung - pathology; Lungs; Medical sciences; Microscopy; Microscopy, Confocal; Necrosis; Pathogenesis; Permeability; Plasma; Poloxamer - pharmacology; Poloxamer - therapeutic use; Proteins; Pulmonary Surfactants - pharmacology; Pulmonary Surfactants - therapeutic use; Random Allocation; Rats; Rats, Sprague-Dawley; Respiratory distress syndrome; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Tumor necrosis factor-TNF; Ventilator-Induced Lung Injury - drug therapy; Ventilator-Induced Lung Injury - pathology; Ventilator-Induced Lung Injury - prevention & control; Ventilators
• ISSN: 1073-449X; 1535-4970
• DOI: 10.1164/rccm.201104-0647oc

Wounded alveolus resident cells are identified in human and experimental acute respiratory distress syndrome models. Poloxamer 188 (P188) is an amphiphilic macromolecule shown to have plasma membrane-sealing properties in various cell types. To investigate whether P188 (1) protects alveolus resident cells from necrosis and (2) is associated with reduced ventilator-induced lung injury in live rats, isolated perfused rat lungs, and scratch and stretch-wounded alveolar epithelial cells. Seventy-four live rats and 18 isolated perfused rat lungs were ventilated with injurious or protective strategies while infused with P188 or control solution. Alveolar epithelial cell monolayers were subjected to scratch or stretch wounding in the presence or absence of P188. P188 was associated with fewer mortally wounded alveolar cells in live rats and isolated perfused lungs. In vitro, P188 reduced the number of injured and necrotic cells, suggesting that P188 promotes cell repair and renders plasma membranes more resilient to deforming stress. The enhanced cell survival was accompanied by improvement in conventional measures of lung injury (peak airway pressure, wet-to-dry weight ratio) only in the ex vivo-perfused lung preparation and not in the live animal model. P188 facilitates plasma membrane repair in alveolus resident cells, but has no salutary effects on lung mechanics or vascular barrier properties in live animals. This discordance may have pathophysiological significance for the interdependence of different injury mechanisms and therapeutic implications regarding the benefits of prolonging the life of stress-activated cells.