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Biophys. J. BioFAST: First Published May 27, 2005. doi:10.1529/biophysj.105.062620
© 2005 by the Biophysical Society.


A more recent version of this article appeared on September 1, 2005.
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Inactivation of Pulmonary Surfactant by Serum: Mechanisms of Reduced Adsorption and its Reversal by Hydrophilic Polymers - Part 1. Experimental

H. William Taeusch 1, Jorge Bernadino de la Serna 2, Jesus Perez-Gil 2, Coralie Alonso 3 and Joseph A. Zasadzinski 4*

1 University of California, San Francisco
2 Universidad Complutense, Madrid
3 University of California, Santa Barbara
4 Univ. of California

* To whom correspondence should be addressed. E-mail: gorilla{at}engineering.ucsb.edu.

Submitted on March 9, 2005
Revised on April 17, 2005
Accepted on 17 May 2005


   Abstract
The rate of change of surface pressure, {pi}, in a Langmuir trough following the deposition of surfactant suspensions on subphases containing serum, with or without polymers, is used to model a likely cause of surfactant inactivation in vivo: inhibition of surfactant adsorption due to competitive adsorption of surface active serum proteins. Aqueous suspensions of native porcine surfactant, organic extracts of native surfactant, and the clinical surfactants Curosurf, Infasurf, and Survanta spread on buffered subphases increase the surface pressure, {pi}, to ~ 40 mN/m within two minutes. The variation with concentration, temperature, and mode of spreading confirmed Brewster angle microscopy (BAM) observations that subphase to surface adsorption of surfactant is the dominant form of surfactant transport to the interface. However (with the exception of native porcine surfactant), similar rapid increases in {pi} did not occur when surfactants were applied to subphases containing serum. Components of serum are surface active and adsorb reversibly to the interface increasing {pi} up to a concentration-dependent saturation value, {pi}max. When surfactants were applied to subphases containing serum, the increase in {pi} was significantly slowed or eliminated below {pi}max. However, the increase in {pi} was rapid, approaching that of a clean interface, above {pi}max. Therefore, serum at the interface presents a barrier to surfactant adsorption, but the barrier is lowered as more surfactant is adsorbed. Addition of either hyaluronan (normally found in alveolar fluid) or polyethylene glycol to subphases containing serum reversed inhibition by restoring the rate of surfactant adsorption to that of the clean interface below {pi}max, thereby allowing surfactant to overcome the serum-induced barrier to adsorption.

Key Words: Curosurf, Survanta, depletion attraction, hyaluronic acid, polyethylene glycol, porcine surfactant




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