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Am J Physiol Lung Cell Mol Physiol (January 10, 2003). doi:10.1152/ajplung.00200.2002
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Submitted on June 24, 2002
Accepted on December 17, 2002

SP-A Is Necessary for Increased Clearance of Alveolar DPPC with Hyperventilation or Secretagogues

Deepika Jain1, Chandra Dodia1, Sandra R. Bates1, Samuel Hawgood2, Francis R. Poulain2, and Aron B. Fisher1*

1 Institute for Environmental Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
2 Department of Pediatrics and Cardiovascular Research Institute, University of California San Francisco, San Francisco, CA, USA

* To whom correspondence should be addressed. E-mail: abf{at}mail.med.upenn.edu.

The role of surfactant protein-A (SP-A) in pulmonary uptake and metabolism of 3H-dipalmitoylphosphatidylcholine (3 H-DPPC) was studied using SP-A gene-targeted mice (SP-A -/-). Unilamellar liposomes were instilled into the trachea of anesthestized mice. Uptake was measured as dpm in lungs plus liver and kidney for in vivo experiments and in lungs and perfusate for isolated lung experiments. 3H-DPPC uptake increased with CO2-induced hyperventilation in wild type mice (SP-A +/+) but was unchanged in SP-A -/-. Secretagogue-treatment approximately doubled the uptake of 3H-DPPC in isolated lungs from SP-A +/+ but had no effect in SP-A -/-. Lungs degraded 23±1.2% of internalized 3H-DPPC in SP-A +/+ and 36 ±0.6% in SP-A -/-; degradation increased with 8-Br cAMP in SP-A +/+ but was unchanged in SP-A -/-. Activity of lysosomal-type phospholipase A2 (aiPLA2) was significantly greater in lungs from SP-A -/- compared to SP-A +/+. Thus, SP-A is necessary for lungs to respond to hyperventilation or secretagogues with increased DPPC uptake and also modulates the PLA2-mediated degradation of internalized DPPC.




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