Lysophosphatidylcholine uptake and metabolism in the adult rabbit lung.
Tracer quantities of 3H-labeled lysoPC and 32P-labeled natural rabbit surfactant were given intratracheally via a bronchoscope and [14C]palmitate was given intravenously to 25 rabbits with labeled PC and lysoPC measured in the alveolar wash, lung homogenate, lamellar bodies and microsomes at five times from 10 min to 6 h after tracheal injection. Surprisingly, only 31% of the administered lysoPC remained in its original form in the total lungs (alveolar wash + lung homogenate) by 10 min, of which 77% was in the alveolar wash. Meanwhile, by 10 min an additional 37% was already converted to PC, of which more than 98% was in the lung homogenate. LysoPC continued to be rapidly and efficiently converted to PC, with 62% conversion measured at 3 h. The converted lysoPC initially appeared with high specific activity in microsomes, then in lamellar bodies, and finally in the alveolar wash. The intravascular palmitate labeled lung PC had similar specific activity-time profiles in the subcellular fractions, while intratracheally administered natural rabbit surfactant had a constantly low specific activity in microsomes and much higher specific activities in lamellar bodies and alveolar wash. Another 25 rabbits received intratracheal lysoPC labeled in both the choline and palmitate moieties and then were studied from 1 to 24 h after tracheal injection. The ratio of the palmitate to choline labels indicated uptake and conversion to PC primarily by direct acylation rather than transacylation and by intact reuptake and conversion rather than breakdown and resynthesis. LysoPC is an attractive 'metabolic probe' of surfactant metabolism which undergoes very rapid and efficient intracellular conversion to PC via a subcellular pathway that parallels the remodeling and de novo synthetic pathways.
Seidner
S R
SR
Department of Pediatrics, Harbor-UCLA Medical Center, UCLA School of Medicine, Torrance 90509.
Jobe
A H
AH
Ikegami
M
M
Pettenazzo
A
A
Priestley
A
A
Ruffini
L
L
D000818:Animals; D001711:Biotransformation; D005260:Female; D008168:Lung / Q000378:metabolism*; D008244:Lysophosphatidylcholines / Q000378:metabolism* / Q000493:pharmacokinetics; D008657:Metabolic Clearance Rate; D008861:Microsomes / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000378:metabolism; D011817:Rabbits; D013347:Subcellular Fractions / Q000378:metabolism; D013997:Time Factors
D008244:Lysophosphatidylcholines; D010743:Phospholipids