Surface activity of a synthetic lung surfactant containing a phospholipase-resistant phosphonolipid analog of dipalmitoyl phosphatidylcholine. Am J Physiol Lung Cell Mol Physiol 285: L550-L559, 2003; 10.1152/ajplung.00346.2002.-Surface activity and sensitivity to inhibition from phospholipase A2 (PLA2), lysophosphatidylcholine (LPC), and serum albumin were studied for a synthetic C16:0 diether phosphonolipid (DEPN-8) combined with 1.5% by weight of mixed hydrophobic surfactant proteins (SP)-B/C purified from calf lung surfactant extract (CLSE). Pure DEPN-8 had better adsorption and film respreading than the major lung surfactant phospholipid dipalmitoyl phosphatidylcholine and reached minimum surface tensions Ͻ1 mN/m under dynamic compression on the Wilhelmy balance and on a pulsating bubble surfactometer (37°C, 20 cycles/min, 50% area compression). DEPN-8 ϩ 1.5% SP-B/C exhibited even greater adsorption and had overall dynamic surface tension lowering equal to CLSE on the bubble. In addition, films of DEPN-8 ϩ 1.5% SP-B/C on the Wilhelmy balance had better respreading than CLSE after seven (but not two) cycles of compression-expansion at 23°C. DEPN-8 is structurally resistant to degradation by PLA2, and DEPN-8 ϩ 1.5% SP-B/C maintained high adsorption and dynamic surface activity in the presence of this enzyme. Incubation of CLSE with PLA2 led to chemical degradation, generation of LPC, and reduced surface activity. DEPN-8 ϩ 1.5% SP-B/C was also more resistant than CLSE to direct biophysical inhibition by LPC, and the two were similar in their sensitivity to biophysical inhibition by serum albumin. These findings indicate that synthetic surfactants containing DEPN-8 combined with surfactant proteins or related synthetic peptides have potential utility for treating surfactant dysfunction in inflammatory lung injury. exogenous surfactants; phospholipid analogs; phospholipase A2; phospholipase resistance; inhibition resistance; diether phosphonolipid; surfactant proteins ENDOGENOUS LUNG SURFACTANT contains functionally important lipids and apoproteins (37), and its activity is compromised when these essential components are chemically degraded or altered. One important cause of such effects is through the action of phospholipases or proteases during inflammatory lung injury. Lytic enzymes of this kind can degrade and inactivate not only endogenous surfactant, but also exogenous lung surfactants used in treating clinical acute lung injury and the acute respiratory distress syndrome (ARDS). All current exogenous surfactant drugs contain substantial contents of glycerophospholipids including 1,2-dipalmitoyl-sn-3-phosphatidylcholine (DPPC), the most prevalent component of endogenous lung surfactant. Phospholipase-induced degradation of glycerophospholipids not only reduces the concentration of active surfactant but also generates byproducts like lysophosphatidylcholine (LPC) and fluid free fatty acids that can further decrease surface activity through biophysical interactions (21, 37, 59). Synthetic exogenous surfactan...

Wool is a multicomponent fiber and fulfills the conditions of a composite structure. The three main components are cuticle, cell membrane complex, and cortex. Cuticle cells and cell membrane complexes have been Isolated and analyzed. The exocuticle displays a quite unusual amino acid composition, namely the simuttaneous presence of cystine cross-links and isopeptie cross-links. An explanation for this unusual result is given. Our investigation of the membranes has confirmed Swift's findings that it is resistant to proteolytic enzymes which can probably be explained by the special arrangement of the lipid and protein layers in the cell membrane complex. X-ray investigations of chemically modified, solvent treated, and stretched keratins have shown that the intermicrofibrillar matrix displays a certain degree of order. The X-ray swelling of the matrix-rich human hair is lower than the swelling of the matrix-poorer keratins mohair and porcupine quill. This fact shows that the original hypothesis of preferential matrix swelling is no longer valid.

This laboratory has previously shown (Anderson, V.C. and Thompson, D.H. (1992) Biochim. Biophys. Acta 1109, 33-42; Thompson, D.H., Gerasimov, O.V., Wheeler, J.J., Rui, Y. and Anderson, V.C. (1996) Biochim. Biophys. Acta 1279, 25-34), that plasmenylcholine (1-alk-1'-enyl-2-palmitoyl-sn-glycero-3-phosphocholine; PlsPamCho) liposomes release hydrophilic contents upon photooxidation or acid-catalyzed hydrolysis. We now report the kinetics and chemical mechanism of the acid-catalyzed reaction and its effect on calcein leakage rates. Hydrolysis of the plasmenylcholine vinyl ether linkage generates fatty aldehydes and 1-hydroxy-2-palmitoyl-sn-glycero-3-phosphocholine (lysolipid); HPLC and 1H-NMR experiments establish that the former is readily air-oxidized to fatty acids, while the latter undergoes rapid acid-catalyzed rearrangement to 1-palmitoyl-2-hydroxy-sn-glycero-3-phosphocholine. Lysolipid formation obeys first order kinetics, yielding observed pseudo-first order rate constants that are pH-dependent. Bimolecular hydrolysis rate constants, k(bi), have also been determined. Calcein release rates from plasmenylcholine liposomes are strongly dependent on both the dihydrocholesterol (DHC) content and the extent of PlsPamCho hydrolysis within the bilayer. DHC-free plasmenylcholine liposomes (38 degrees C, pH 2.5) require < 5% PlsPamCho hydrolysis to effect > 50% calcein release within 10 min. The presence of > or = 25 mol% DHC, however, greatly reduces the observed calcein release rate; nearly 30% PlsPamCho hydrolysis is required to effect 50% calcein release over a 70-min period in 6:4 PlsPamCho/DHC liposomes. Bacteriochlorophyll a-sensitized photooxidation of plasmenylcholine liposomes also produces fatty aldehyde and another intermediate, tentatively described as 1-formyl-2-palmitoyl-sn-glycero-3-phosphocholine, that hydrolyzes to form the 1-hydroxy lysolipid. These results have important implications for the quantitative description of lysolipid effects on membrane permeability and on the design of triggerable liposomes for drug delivery.

No abstract