Abstract
Free radicals (FRs) and serum proteins have both been implicated in the pathophysiology of surfactant dysfunction during acute lung injury (ALI). This study examines how these 2 distinct mechanisms interact to contribute to altered surfactant function in this setting. Calf lung surfactant (2 mg/mL) was incubated with no additives (C = control), and with low = (LD = 125 μ M FeCl 2 ; 250 μ M H 2 O 2) and high-dose (HD = 250 μ M FeCl 2 500 μ M H 2 O 2) Fenton reaction reagents to generate hydroxyl radical. Each condition was studied with (1) no protein (N); and with 25%, 200%, and 800% (weight protein/weight phospholipid) protein added as (2) bovine albumin, (3) bovine fibrinogen, (4) hemoglobin, or (5) calf serum. Lipid (LFR) and protein (PFR) free-radical products, and modifications in the tertiary structure of Surfactant Protein A(SPA) on Western blot, were observed in NLD and NHD samples. Added proteins reduced PFR changes as well as SPA structural changes. Protection was greatest for fibrinogen, hemoglobin, and serum, and least for albumin. Minimal to no dysfunction, assayed by pulsating surfactometry, was observed in all samples. These findings indicate that addition of serum proteins to surfactant at 2 mg/mL protects against, rather than promotes, FR-mediated chemical changes in surfactant lipid and protein constituents.