Role of lipid polymorphism in pulmonary surfactant

Science

Volumn 273, Issue 5273, 1996, Pages 330-332

  Perkins, Walter R ^a   Dause, Richard B ^a   Parente, Roberta A ^a,d   Minchey, Sharma R ^a   Neuman, Keir C ^b   Gruner, Sol M ^b   Taraschi, Theodore F ^c   Janoff, Andrew S ^a  

^a Liposome Company Incorporated   (United States)

^b PRINCETON UNIVERSITY   (United States)

^c THOMAS JEFFERSON UNIVERSITY   (United States)

^d Ortho McNeil Pharmaceutical Incorporated   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

LIPOSOME; LUNG SURFACTANT;

ARTICLE; BILAYER MEMBRANE; CELL SPREADING; GENE REARRANGEMENT; GENETIC POLYMORPHISM; GEOMETRY; HYDRATION; LIPID METABOLISM; PRIORITY JOURNAL; RESPIRATORY DISTRESS SYNDROME;

EID: 0029950675     PISSN: 00368075     EISSN: None     Source Type: Journal    
DOI: 10.1126/science.273.5273.330     Document Type: Article

References (47)

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19. h.
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41. Spectra were acquired on a Bruker AM360 NMR spectrometer operating at 145.8 MHz (8.5 T) on nonspinning samples with a 10-mm double-resonance probe. The resonance of small unilamellar vesicles of egg lecithin was used as an external chemical shift reference (0 ppm).
42. Data on x-ray diffraction intensity versus scattering angle were obtained with a two-dimensional (2D) image-intensified x-ray detector, as described [S. M. Gruner, R. P. Lenk, A. S. Janoff, M. J. Ostro, Biochemistry 24, 2833 (1985)]. Samples were spun for 1 hour in a Beckman J2-21 centrifuge at 20,000g to settle the liposomes. The clear supernatant was decanted, and the resultant concentrated liposome suspension was sealed in thinwalled glass x-ray capillaries (diameter 1.5 mm). The capillaries were inserted into the thermostated (±0.5°C) copper jacket of the x-ray specimen stage. The resultant 2D powder diffraction patterns were azimuthally integrated and are displayed as x-ray intensity versus angle from the center of the diffraction pattern. The diffraction spacings were calibrated against silver stearate (long spacing, 48.68 Å).
43. 2 and room temperature before dialysis, subsequent differential scanning calorimetry of samples not frozen and thawed indicated that the lipids were mixed ideally, and the freeze-thaw step was omitted. After dialysis, the liposomes were stored at 5°C until use.
44. We used the mini-Langmuir trough (KSV Instruments, 7.5 cm by 30 cm) equipped with a Wilhelmy balance and a dual-barrier mechanism. Barriers were composed of Delrin, a hydrophilic material that allowed solution contact when the liquid level was ∼1 mm below the edge of the trough. Keeping the solution below the edge of the trough aided greatly our ability to compress DPPC-containing monolayers to very high values of II (low values of γ) by avoiding overflow.
45. Rabbits (∼30 g) were dosed with either 0.2 or 0.3 ml of MLVs passed through a 5-μm filter at a lipid concentration of 20 mg/ml (∼140 to 200 mg per kilogram of body weight). Lung compliance was measured with constant-volume ventilation. Differences between mean dynamic lung compliance were tested with a one-way analysis of variance and Newmann-Keuls multiple-range testing.
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47. We thank G. Heldt for testing of our formulations in the animal model and G. Weissmann for critical reading of the manuscript.