Interaction of C-reactive protein with pulmonary surfactant

McEachren, Todd Mervyn (1996) Interaction of C-reactive protein with pulmonary surfactant. Masters thesis, Memorial University of Newfoundland.

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Abstract

The influence of the acute inflammatory phase protein human C-reactive protein (CRP) on the adsorption of porcine pulmonary surfactant from a subphase into the air-water interface with and without dynamic surface compression has been investigated. CRP was shown to detract from the ability of surfactant to rapidly adsorb to the air-water interface at a molar ratio of 0.03 : 1, protein to phospholipid (weight ratio, 0.5 : 1). On a weight basis, CRP was found to be more effective than fibrinogen or globulin at reducing the adsorption rate of surfactant. The effect of CRP required the presence of calcium, and was reversed by the addition of phosphocholine, in a concentration dependent manner. The inhibition of surfactant adsorption by CRP was effectively eliminated by the addition of phosphocholine at a molar ratio of 300 : 1, phosphocholine : CRP, but it was not diminished by the addition of identical molar ratios of o-phosphoethanolamine or DL-α-glycerophosphate at the same molar ratios. These data suggest that the potent inhibition of surfactant adsorption by CRP is primarily a result of a specific interaction between CRP and the phosphocholine headgroup of surfactant lipids in the subphase and that it can be reversed by the water-soluble CRP ligand, phosphocholine. Experiments were performed to determine the effect of the addition of the complement protein C1q on the adsorption of porcine lipid extract pulmonary surfactant from the subphase to the air-water interface with and without dynamic compression. C1q, at a weight ratio of 10% (C1q : PL), when added to lipid extract surfactant, which is void of SP-A, increased the adsorption rate of the lipid extract surfactant to approach the rate at which whole surfactant, which contains 5-7% SP-A, by weight. C1q at this weight ratio did not detract from the ability of lipid extract surfactant from attaining a minimum surface tension under dynamic compression. Albumin, when added to lipid extract surfactant at the identical weight ratio at which C1q was a added, detracted from the ability of lipid extract surfactant to adsorb to the air-water interface. Albumin, also detracted from the ability of this mixture in attaining a minimum surface tension under dynamic compression. This suggests that C1q, which shares quaternary structural homology with SP-A, increases the adsorption of lipid extract surfactant by a similar molecular interaction as that of SP-A. Serum CRP levels, expressed μg/ml and as percentage of total protein, were elevated in patients with ARDS and those patients at risk of ARDS compared to normals. A weak correlation exists between the serum CRP in ICU patients, expressed as percentage of total protein and the APACHE II score. This suggests that CRP levels may be useful in the clinical evaluation of patients in the ICU.

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