title: Lung function in premature rabbits treated with recombinant human surfactant protein-C.
abstract: We report the activity of recombinant human surfactant apoprotein-C (rSP-C[Cys]2) and various phospholipids in a preterm rabbit model of respiratory distress syndrome (RDS). Mixtures of rSP-C(Cys)2 and certain phospholipids had similar activity (lung compliance and lung pressure-volume behavior) to rabbit surfactant in this model. The activity of rSP-C(Cys)2 was maximal at 1 mol% protein and varied significantly with the phospholipid composition. Chemically synthesized SP-C had similar activity to rSP-C(Cys)2. Deletion of six amino-terminal residues did not affect function. Substitution of cysteines and cysteine6 with adjacent serines (rSP-C[Ser]2) by site-specific mutagenesis minimized aggregation of rSP-C but did not affect activity. Palmitoylation of cysteine5 and cysteine6 in rSP-C (rSP-C[C16]2) did not enhance the activity of rSP-C(Cys)2. We conclude that bacterial expression is a practical source of functional SP-C, and that nonacylated forms of SP-C may be useful adjuvants to phospholipids in the treatment of RDS and possibly other forms of acute lung injury.
authors: Cardiovascular Research Institute, University of California, San Francisco 94143-0130, USA.
authors: S
authors: S
authors: Hawgood
authors: A
authors: A
authors: Ogawa
authors: K
authors: K
authors: Yukitake
authors: M
authors: M
authors: Schlueter
authors: C
authors: C
authors: Brown
authors: T
authors: T
authors: White
authors: D
authors: D
authors: Buckley
authors: D
authors: D
authors: Lesikar
authors: B
authors: B
authors: Benson
mesh_terms: D000818:Animals; D006801:Humans; D007231:Infant, Newborn; D008168:Lung / Q000503:physiopathology*; D010743:Phospholipids / Q000737:chemistry / Q000627:therapeutic use; D011510:Proteolipids / Q000737:chemistry / Q000627:therapeutic use*; D011663:Pulmonary Surfactants / Q000737:chemistry / Q000627:therapeutic use*; D011817:Rabbits; D011994:Recombinant Proteins / Q000737:chemistry / Q000627:therapeutic use; D012127:Respiratory Distress Syndrome, Newborn / Q000188:drug therapy* / Q000503:physiopathology
chemical_list: D010743:Phospholipids; D011510:Proteolipids; D011663:Pulmonary Surfactants; D011994:Recombinant Proteins