Surfactant protein-C in ventilated premature lamb lung.
Although surfactants containing only lipids and surfactant protein C (SP-C) or SP-C analogs can be effective for the treatment of surfactant deficiency in animal models, there is no information concerning the alveolar or lung clearance of SP-C. Because the other lipid and protein components of surfactant are cleared very slowly from the preterm lung, we hypothesized that SP-C also would be cleared slowly. Therefore, we compared the losses of iodinated native SP-C (nSP-C) and a recombinant SP-C analog (rSP-C, phenylalanines in positions 4 and 5 and isoleucine in position 32 of the human sequence) to [14C]dipalmitoylphosphatidylcholine (DPPC) after airway administration at birth of trace or treatment doses of surfactant given to preterm lambs. In preterm lambs given trace doses at 134-136 d gestation, alveolar [14C]DPPC and [125I]rSP-C decreased to 14.7% recovery for DPPC and 8.3% recovery for rSP-C after 2 h ventilation. There was no loss of [14C]DPPC from the total lungs (alveolar wash + lung tissue), and approximately 20% of the [125I]rSP-C was lost from the lungs. For 128 d gestational age lambs treated with 100-mg/kg doses of surfactants containing nSP-C or 2% rSP-C, the alveolar and total lung recoveries for [125I]nSP-C or [125I]rSP-C were equivalent to that of [14C]DPPC after 5 h ventilation. These results demonstrate that nSP-C and rSP-C have alveolar clearances and accumulations into preterm lung tissue that are similar to those of DPPC.
Ikegami
M
M
Children's Hospital Medical Center, Division of Pulmonary Biology, Cincinnati, Ohio 45229-3039, USA.
Jobe
A H
AH
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000008:administration & dosage / Q000493:pharmacokinetics; D000818:Animals; D000831:Animals, Newborn; D004195:Disease Models, Animal; D006801:Humans; D007231:Infant, Newborn; D008168:Lung / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D011510:Proteolipids / Q000008:administration & dosage / Q000378:metabolism* / Q000493:pharmacokinetics; D011650:Pulmonary Alveoli / Q000378:metabolism; D011663:Pulmonary Surfactants / Q000008:administration & dosage / Q000378:metabolism* / Q000493:pharmacokinetics; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics; D012127:Respiratory Distress Syndrome, Newborn / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D012756:Sheep
D011510:Proteolipids; D011663:Pulmonary Surfactants; D011994:Recombinant Proteins; D015060:1,2-Dipalmitoylphosphatidylcholine