Restoration of surfactant activity by polymyxin B in lipopolysaccharide-potentiated injury of immature rabbit lungs. 2021

Andrea Calkovska, and Marie Haegerstrand-Björkman, and Tore Curstedt
Laboratory for Surfactant Research, Department of Molecular Medicine and Surgery, Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden. andrea.calkovska@uniba.sk.

During postnatal adaptation pulmonary surfactant may be inactivated by lipopolysaccharide (LPS). We evaluated the effect of surfactant therapy in combination with antibiotic polymyxin B (PxB) in double-hit model of neonatal lung injury. Surfactant (poractant alfa, Curosurf) was exposed to smooth (S) LPS without/with PxB and tested in captive bubble surfactometer. Preterm rabbits received intratracheally saline (control) or S-LPS and were ventilated with 100% oxygen. After 30 min, LPS-treated animals received no treatment, or surfactant (200 mg/kg) without/with 3% PxB; controls received the same dose of surfactant. Animals were ventilated for further 2 h. In vitro, addition of 5% S-LPS to surfactant increased minimum surface tension (γmin) and addition of 1-3% PxB to surfactant/S-LPS mixture restored γmin to low values. Animals only given S-LPS had lower lung compliance and lung gas volume (LGV) compared to surfactant groups. Treatment with surfactant/PxB, but not with surfactant only, restored LGV. Addition of PxB to the surfactant increased the alveolar expansion. S-LPS interferes with surface activity of the pulmonary surfactant and PxB improves the resistance of surfactant to LPS-induced inactivation. In our neonatal model of respiratory distress syndrome surfactant gives positive response even in simultaneous exposure to S-LPS, when enriched with PxB.

UI MeSH Term Description Entries
D007231 Infant, Newborn An infant during the first 28 days after birth. Neonate,Newborns,Infants, Newborn,Neonates,Newborn,Newborn Infant,Newborn Infants
D008070 Lipopolysaccharides Lipid-containing polysaccharides which are endotoxins and important group-specific antigens. They are often derived from the cell wall of gram-negative bacteria and induce immunoglobulin secretion. The lipopolysaccharide molecule consists of three parts: LIPID A, core polysaccharide, and O-specific chains (O ANTIGENS). When derived from Escherichia coli, lipopolysaccharides serve as polyclonal B-cell mitogens commonly used in laboratory immunology. (From Dorland, 28th ed) Lipopolysaccharide,Lipoglycans
D008168 Lung Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood. Lungs
D008170 Lung Compliance The capability of the LUNGS to distend under pressure as measured by pulmonary volume change per unit pressure change. While not a complete description of the pressure-volume properties of the lung, it is nevertheless useful in practice as a measure of the comparative stiffness of the lung. (From Best & Taylor's Physiological Basis of Medical Practice, 12th ed, p562) Compliance, Lung,Compliances, Lung,Lung Compliances
D008297 Male Males
D010743 Phospholipids Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides see GLYCEROPHOSPHOLIPIDS) or sphingosine (SPHINGOLIPIDS). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. Phosphatides,Phospholipid
D011112 Polymyxin B A mixture of polymyxins B1 and B2, obtained from BACILLUS POLYMYXA strains. They are basic polypeptides of about eight amino acids and have cationic detergent action on cell membranes. Polymyxin B is used for treatment of infections with gram-negative bacteria, but may be neurotoxic and nephrotoxic. Aerosporin,Polymyxin B Sulfate
D011663 Pulmonary Surfactants Substances and drugs that lower the SURFACE TENSION of the mucoid layer lining the PULMONARY ALVEOLI. Surfactants, Pulmonary,Pulmonary Surfactant,Surfactant, Pulmonary
D012127 Respiratory Distress Syndrome, Newborn A condition of the newborn marked by DYSPNEA with CYANOSIS, heralded by such prodromal signs as dilatation of the alae nasi, expiratory grunt, and retraction of the suprasternal notch or costal margins, mostly frequently occurring in premature infants, children of diabetic mothers, and infants delivered by cesarean section, and sometimes with no apparent predisposing cause. Infantile Respiratory Distress Syndrome,Neonatal Respiratory Distress Syndrome,Respiratory Distress Syndrome, Infant
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal

Related Publications

Andrea Calkovska, and Marie Haegerstrand-Björkman, and Tore Curstedt
June 2007, Chinese journal of traumatology = Zhonghua chuang shang za zhi,
Andrea Calkovska, and Marie Haegerstrand-Björkman, and Tore Curstedt
April 1995, The American journal of physiology,
Andrea Calkovska, and Marie Haegerstrand-Björkman, and Tore Curstedt
July 2018, International journal of molecular sciences,
Andrea Calkovska, and Marie Haegerstrand-Björkman, and Tore Curstedt
November 1985, Biochemical pharmacology,
Andrea Calkovska, and Marie Haegerstrand-Björkman, and Tore Curstedt
January 1996, Laboratory investigation; a journal of technical methods and pathology,
Andrea Calkovska, and Marie Haegerstrand-Björkman, and Tore Curstedt
April 1990, Journal of applied physiology (Bethesda, Md. : 1985),
Andrea Calkovska, and Marie Haegerstrand-Björkman, and Tore Curstedt
June 2018, Journal of the American Chemical Society,
Andrea Calkovska, and Marie Haegerstrand-Björkman, and Tore Curstedt
June 1991, Drug and therapeutics bulletin,
Andrea Calkovska, and Marie Haegerstrand-Björkman, and Tore Curstedt
October 1986, British journal of experimental pathology,
Andrea Calkovska, and Marie Haegerstrand-Björkman, and Tore Curstedt
March 1995, Journal of applied physiology (Bethesda, Md. : 1985),
Copied contents to your clipboard!