REACTIVE OXYGEN SPECIES INACTIVATION OF SURFACTANT INVOLVES STRUCTURAL AND FUNCTIONAL ALTERATIONS TO SURFACTANT PROTEINS SP-B AND SP-C

¹ University of Western Ontario

^* To whom correspondence should be addressed. E-mail: fpossmay{at}uwo.ca.

Submitted on August 24, 2005
Revised on September 20, 2005
Accepted on 5 January 2006

	Abstract

Exposing BLES, a clinical surfactant, to reactive oxygen species (ROS) arising from hypochlorous acid or the Fenton reaction resulted in an increase in lipid (conjugated dienes, lipid aldehydes) and protein (carbonyls) oxidation products and a reduction in surface activity. Experiments where oxidized phospholipids (PL) were mixed with BLES demonstrated this addition hampered BLES biophysical activity. However the effects were only moderately greater than with control PL. These results imply a critical role for protein oxidation. BLES oxidation by either method resulted in alterations in surfactant proteins, SP-B and SP-C, as evidenced by altered Coomassie blue and silver staining. Western blot analyses showed depressed reactivity with specific antibodies. Oxidized SP-C showed decreased palmitoylation. Reconstitution experiments employing PL, SP-B, and SP-C isolated from control or oxidized BLES demonstrated protein oxidation was more deleterious than lipid oxidation. Furthermore, addition of control SP-B improved samples containing SP-C, but not vice versa. We conclude surfactant oxidation arising from ROS generated by air pollution or leukocytes interferes with surfactant function through oxidation of surfactant PL and proteins, but that protein oxidation, in particular SP-B modifications, produces the major deleterious effects.

Key Words: captive bubble surfactometer, pulmonary surfactant inhibition, reactive oxygen species, surface tension, surfactant phospholipids, surfactant proteins

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