Surfactant associated proteins

The reason(s) for the difference in equilibrium surface tensions of airway and alveolus are unknown, but they may reflect differences in the composition, concentration, or both, of the surfactant of the two compartments. As the rate of adsorption of lipids to the film interface depends on both the composition and concentration of the surfactant phospholipids and the associated surfactant proteins (23,65), the low SP-A and absent SP-B and SP-C in the pig tracheal fluid in the foregoing experiments (44) may account for the higher static adsorptions observed in the tracheal fluids from this species. 

The well-defined helical structure associated with appropriately substituted peptoid oligomers (Section 1.6) can be employed to fashion compounds that closely mimic the stracture and function of certain bioactive peptides. There are many examples of small helical peptides (<100 residues) whose mimicry by non-natural ohgomers could potentially yield valuable therapeutic and bioactive compounds. This section describes peptoids that have been rationaUy designed as mimics of antibacterial peptides, lung surfactant proteins, and coUagen proteins. Mimics of HIV-Tat protein, although relevant to this discussion, were described previously in this chapter (Sections 1.3.2 and 1.4.1). 

Polymer/Surfactant Interactions. Interaction between polymers and surfactants was recently reviewed by Robb (11) and surfactant association with proteins by Steinhardt and Reynolds (12). Polymer/surfactant interactions are highly dependent on the chemical nature of the polymer and the surfactant. In general, surfactants tend to associate with uncharged polymers in aggregates rather than individual surfactant molecules interacting with the macro-molecule. The ability of surfactants to form micelles is thought to be an important factor in the role of surfactant behavior in interactions with polymers. Individual surfactant... 

It is well established that surfactants can associate with proteins to form molecular complexes involving various kinds of attractive interactions (Coke et ah, 1990 Bos et al., 1997 Bos and van Vliet, 2001 Kelley and McClements, 2003 Semenova et al., 2003, 2006 IE in et al., 2004, 2005 Malhotra and Coupland, 2004 Istarova et al., 2005 Semenova, 2007). The role of protein-surfactant complexes is a more important issue with charged surfactants. As a consequence of complexation, a mixed system of protein + surfactant may have completely different surface activity and rheological properties from those of the pure protein or the pure surfactant (see section 2 in chapter six for more details). 

Lausen, M., Lynch, N., Schlosser, A., Tornoe, I., Sackmose, S. G., Teisner, B., Willis, A. C., Crouch, E., Schwaeble, W., and Holmskov, U. (1999). Microfibril-associated protein 4 is present in lung washings and binds to the collagen region of lung surfactant protein D. / Biol. Chem. 274, 32234-32240. 

Some proteins self-associate in aqueous solution to form oligomers. Insulin, for example, exists in several associated states the zinc hexamer of insulin is a complex of insulin and zinc which dissolves slowly into dimers and eventually monomers following its subcutaneous administration, so giving it long-acting properties. In most cases, however, it is desirable to prevent association such that only monomeric or dimeric forms are present in the formulations and a more rapid absorption is achieved. Recent studies have been directed towards engineering insulin molecules which are not prone to association, " or the prevention of association through the addition of surfactants. Protein self-association is a reversible process, i.e. alteration of the solvent properties can lead to the re-formation of the monomeric native protein. There is an important distinction between this association... 

In adults, a severe form of lung injury can develop in association with sepsis, pneumonia, and injury to the lungs due to trauma or surgery. This catastrophic disorder is known as acute respiratory distress syndrome (ARDS) and has a mortality rate of more than 40%. In ARDS, one of the major problems is a massive influx of activated neurophils which damage both vascular endothelium and alveolar epithelium and result in massive pulmonary edema and impairment of surfactant function. Neutrophil proteinases (e.g., elastase) break down surfactant proteins. A potential therapeutic strategy in ARDS involves administration of both surfactant and antiproteinases (e.g., recombinant a I -antitrypsin). 

Choudhury AH, Gordian ME, Morris SS (1997) Associations between respiratory illness and PMio air pollution. Arch Environ Health 52 113-117 Ciencewicki J, Gowdy K, Krantz QT et al (2007) Diesel exhaust enhanced susceptibility to influenza infection is associated with decreased surfactant protein expression. Inhal Toxicol 19 1121-1133... 

Some results and conclusions presented are the outcome of several years of fruitful collaborations with C. Prata (synthesis of azo derivatives), G. Pouliquen, J. Ruchmann and I. Porcar (physical-chemistry investigations on association with proteins or surfactants), and S. Khoukh and P. Perrin (development of photoemulsifiers). 

Emulsions are dispersions of one liquid in another liquid, most commonly water-in-oil or oil-in-water. The total interfacial area in an emulsion is very large, and sinee flie interfacial area is associated with a positive free energy (the interfacial tension), the emulsion system is thermodjmam-ically unstable. Nevertheless, it is possible to make emulsions with an excellent long-term stability. This requires the use of emulsifiers that accumulate at the oil/water interface and create an energy barrier towards flocculation and coalescence. The emulsifiers can be ionic, zwitterionic, or nonionic surfactants, proteins, amphiphilic polymers, or combinations of polymers and surfactants. The structure of the adsorbed layer at the water/oil interface may be rather complex, involving several species adsorbed directly to the interface as well as other species adsorbing on top of the first layer. 

Surfactant protein D" " mice demonstrated increased numbers of airway- and vessel-associated lymphocytes without increases in interstitial lymphocytes (Fisher et al. 2002). There was increased proliferative activity of lymphocytes isolated by enzymatic dissociation of minced lung. There was marked T-cell activation in the lungs of surfactant protein D" mice, as reflected by an increased percentage of both CD4 and CD8 T cells expressing CD69 and CD25. 

Curosurf (Chiesi Farmaceutici, Parma, Italy) is a natural surfactant extract, prepared from porcine lung, containing almost exclusively polar lipids, in particular phosphatidylcholine (about 70% of total phospholipid content), phospha-tidylglycerol (about 30% of total phospholipids content) and about 1% of surfactant associated hydrophobic proteins SP-B and SP-C. The surfactant was suspended in 0.9 % sodium chloride solutiOTi. The pH was adjusted as required... 

Surfactant, pulmonary-associated protein C (surfactant protein C)... 

Nogee LM, Dunbar AE III, Wert SE, et al. A mutation in the surfactant protein C gene associated with familial interstitial lung disease. N Engl J Med 2001 344(8) 573-579. 

Thomas AQ, Lane K, Phillips J HI, et al. Heterozygosity for a surfactant protein C gene mutation associated with usual interstitial pneumonitis and cellular nonspecific interstitial pneumonitis in one kindred. Am J Respir Crit Care Med 2002 165(9) 1322-1328. 

DIP usually affects adults age at onset of symptoms is generally 30 to 50 years (8,10,17). Approximately 80% to 90% of patients with DIP are active smokers or have smoked in the past (8,10,17,18). There have been cases of DIP associated with connective tissue diseases, viral infections (e.g., hepatitis C), occupational/ environmental exposures, and drugs (e.g., nitrofurantoin) (17-21). In addition, a lesion resembling DIP has been described in infants with mutations in the surfactant protein C gene (22). 

Such interactions are directly relevant to the effect of surfactants on drug absorption. Fig. 10.5a shows the relationship between absorption of salicylate or L-valine across rat jejunal tissue in vivo and release of protein and phospholipid by a series of surfactants. Fig. 10.5b shows the relative activity of a series of non-ionic surfactants of the Brij series and sodium taurodeoxycholic acid (NaTDC), sodium dodecyl sulphate (NaDS) and CTAB [30]. An association between protein release and increased absorption of solutes has also been reported by Feldman and Reinhard [31] and Walters et al. [32]. Anionic, non-ionic and cationic surfactants tended to accelerate the breakdown of the mucous layer covering the epithelium and at high concentrations were thought to interfere with the structure of the mucosal surface itself. Exposure of various anionic and nonionic surfactants to rabbit intestinal mucosa causes epithelial desquamation and necrosis [33]. 

Collectins are a family of C-type lectins that mediate host defense against pathogenic micro-organisms. Each collectin polypeptide is characterized by an N-terminal collagen-like region and a C-terminal C-type CRD [1]. Six members of the collectin family have been identified in vertebrates. Serum MBP, collectin-43 (CL-43) and conglutinin are plasma proteins, liver MBP is found exclusively in the liver and pulmonary surfactant proteins-A and -D (SP-A, SP-D) are associated with the surfactant that lines alveoli in the lung. 

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