Surfactant apoprotein A modifies the inhibitory effect of plasma proteins on surfactant activity in vivo.
Surfactant apoprotein A (SP-A) reduces the inhibitory effects of plasma proteins on the surface tension lowering properties of pulmonary surfactant in vitro. To test the effects of SP-A in vivo we administered a complete natural dog lung surfactant (DLS) containing apoproteins SP-A, SP-B, and SP-C, a butanol extract of DLS (DLSE) containing only apoproteins SP-B and SP-C, and DLSE supplemented with SP-A intratracheally to prematurely delivered rabbit pups in the presence of increasing amounts of human plasma. In the absence of plasma DLS and DLSE (100 mg/kg phospholipid) had comparable effects on lung mechanics (compliance during ventilation with a tidal volume of 6-7 mL/kg and quasi-static pressure-volume behavior) in this surfactant deficiency model. Plasma proteins in increasing amounts to a maximum protein concentration of 62.5 mg/mL had no effect on the response of the pups to DLS. In contrast, plasma added to DLSE in concentrations above 20 mg/mL significantly increased the peak inspiratory pressure (PIP) required to ventilate the pups with a tidal volume of 6-7 mL/kg, reduced the calculated total lung compliance, and decreased the deflation lung volumes. The inhibitory effects of plasma on DLSE were significantly less when SP-A was added to DLSE (5:1, phospholipid:SP-A, wt:wt). The addition of SP-A to DLSE in plasma restored the activity of the extract to levels comparable to complete DLS. These results suggest that plasma can interfere with surfactant function and that SP-A has a significant protective effect for surfactant against the inhibitory effects of plasma in vivo.
Yukitake
K
K
Cardiovascular Research Institute, University of California, San Francisco 94143.
Brown
C L
CL
Schlueter
M A
MA
Clements
J A
JA
Hawgood
S
S
D000818:Animals; D000831:Animals, Newborn; D001059:Apoproteins / Q000302:isolation & purification / Q000494:pharmacology*; D001798:Blood Proteins / Q000494:pharmacology*; D004285:Dogs; D005260:Female; D006801:Humans; D008170:Lung Compliance / Q000187:drug effects / Q000502:physiology; D008176:Lung Volume Measurements; D011247:Pregnancy; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000302:isolation & purification / Q000378:metabolism* / Q000494:pharmacology*; D011817:Rabbits; D015656:Respiratory Mechanics / Q000187:drug effects / Q000502:physiology
D001059:Apoproteins; D001798:Blood Proteins; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants; C046616:pulmonary surfactant apoprotein