Surfactant inhibition by plasma proteins: differential sensitivity of various surfactant preparations.
Leakage of plasma proteins into the alveolar space may inhibit surfactant function. We compared the surface properties and the sensitivity to inhibitory proteins of different organic solvent surfactant extracts and a synthetic surfactant. Experiments were performed in the pulsating bubble surfactometer, with surfactant concentrations ranging between 0.1 and 2 mg.ml-1. Inhibition profiles towards fibrinogen, albumin and haemoglobin were obtained from calf lung surfactant extracts (CLSE), Alveofact, Curosurf and Survanta (all used in clinical, replacement studies in respiratory distress syndrome (RDS) and of an apoprotein-based synthetic phospholipid mixture (PLM-C/B; DPPC:PG:PA = 68.5:22.5:9, supplemented with 2% wt/wt non-palmitoylated human recombinant SP-C and 1% t/wt natural bovine SP-B). In the absence of inhibitory proteins, all surfactants exhibited dose-dependent rapid adsorption (rank order of relative efficacy PLM-C/B = CLSE > Alveofact > Curosurf > Survanta). Minimal surface tension was reduced to near zero values under dynamic compression (rank order PLM-C/B > CLSE > Alveofact = Curosurf) and to approximately 4 mN.m-1 (Survanta). Curosurf and Survanta were dose-dependently inhibited by fibrinogen > haemoglobin > albumin, with far-reaching loss of surface activity at protein-surfactant ratios above 1:1. In contrast, CLSE and Alveofact were only moderately inhibited by fibrinogen, and were not affected by haemoglobin and albumin, up to protein-surfactant ratios of 2:1. PLM-C/B exhibited resistance to fibrinogen, intermediate sensitivity to albumin, and was severely inhibited by haemoglobin. We conclude that various natural surfactant extracts and an apoprotein-based synthetic surfactant mixture markedly differ in their sensitivity to inhibitory plasma proteins.(ABSTRACT TRUNCATED AT 250 WORDS)
Seeger
W
W
Dept of Internal Medicine, Justus-Liebig-University Giessen, Germany.
Grube
C
C
Günther
A
A
Schmidt
R
R
D000818:Animals; D001688:Biological Products; D001798:Blood Proteins / Q000494:pharmacology*; D002417:Cattle; D006801:Humans; D066298:In Vitro Techniques; D007231:Infant, Newborn; D008055:Lipids; D010743:Phospholipids; D011663:Pulmonary Surfactants / Q000037:antagonists & inhibitors / Q000627:therapeutic use; D012127:Respiratory Distress Syndrome, Newborn / Q000628:therapy; D013500:Surface Tension
D001688:Biological Products; D001798:Blood Proteins; D008055:Lipids; D010743:Phospholipids; D011663:Pulmonary Surfactants; C078272:SF-RI 1, bovine surfactant preparation; C068291:poractant alfa; C072197:beractant