Comparison of three lipid formulations for synthetic surfactant with a surfactant protein B analog.
Surfactant protein B (SP-B) is an essential component of pulmonary surfactant. Synthetic dimeric SP-B(1-25) (SP-B(1-25)), a peptide based on the N-terminal domain of human SP-B, efficiently mimics the functional properties of SP-B. The authors investigated the optimum lipid composition for SP-B(1-25) by comparing the effects of natural lung lavage lipids (NLL), a synthetic equivalent of NLL (synthetic lavage lipids SLL), and a standard lipid mixture (TL) on the activities of SP-B(1-25). Surfactant preparations were formulated by mixing 2 mol% SP-B(1-25) in NNL, SLL, and TL. Calfactant, a calf lung lavage extract with SP-B and SP-C, was a positive control and lipids without peptide were negative controls. Minimum surface tension measured on a captive bubble surfactometer was similar for the three SP-B(1-25) surfactant preparations and calfactant. The effects on lung function were compared in ventilated, lavaged, surfactant-deficient rats. Oxygenation and lung volumes were consistently higher in rats treated with calfactant and SP-B(1-25) in NLL or SLL than in rats treated with SP-B(1-25) in TL. Fourier transform infrared spectra observed abnormal secondary conformations for SP-B(1-25) in TL as a possible cause for the reduced lung function. Lipid composition plays a crucial role in the in vitro and in vivo functions of SP-B(1-25) in surfactant preparations.
Walther
Frans J
FJ
Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California 90502, USA. fjwalther@aol.com
Hernández-Juviel
José M
JM
Gordon
Larry M
LM
Waring
Alan J
AJ
Stenger
Patrick
P
Zasadzinski
Joseph A
JA
D000595:Amino Acid Sequence; D000818:Animals; D001688:Biological Products / Q000494:pharmacology; D006801:Humans; D008055:Lipids / Q000032:analysis; D008168:Lung / Q000187:drug effects*; D008176:Lung Volume Measurements; D008297:Male; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000494:pharmacology; D037701:Pulmonary Surfactant-Associated Protein B / Q000138:chemical synthesis* / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017550:Spectroscopy, Fourier Transform Infrared
D001688:Biological Products; D008055:Lipids; D010446:Peptide Fragments; D037701:Pulmonary Surfactant-Associated Protein B; C117342:calfactant