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Editor,—In his leading article Hills reviews important concepts about a “hydrophobic mucosal barrier” as the main biological basis for protecting the stomach against acid mediated damage to the mucosa (Gut 1996; 39: 621–4). While we support the author’s view that lipid rather than mucus makes the gastric surface less vulnerable to protons, the proposed analogy of this “hydrophobic mucosal barrier” with lung surfactant is supported by little direct evidence. Hills claims that the key molecule of lung surfactant, dipalmitoyl phosphatidylcholine (DPPC), is also the main factor of gastric surfactant, based on indirect measurements some 20 years ago.1
Editor,—In his leading article Hills reviews important concepts about a “hydrophobic mucosal barrier” as the main biological basis for protecting the stomach against acid mediated damage to the mucosa (Gut 1996; 39: 621–4). While we support the author’s view that lipid rather than mucus makes the gastric surface less vulnerable to protons, the proposed analogy of this “hydrophobic mucosal barrier” with lung surfactant is supported by little direct evidence. Hills claims that the key molecule of lung surfactant, dipalmitoyl phosphatidylcholine (DPPC), is also the main factor of gastric surfactant, based on indirect measurements some 20 years ago.1
We have recently re-examined this central tenant of the gastric surfactant theory, and have conclusively demonstrated the virtually complete absence of DPPC in gastric mucus lipid. In these studies2 ,3 we extracted the phospholipids from gastric tissue and mucus with chloroform:methanol and determined the compositions of both phospholipid classes and phosphatidylcholine molecular species with two recently developed HPLC techniques, using post-column formation of fluorescent mixed micelles in the presence of 1,6-diphenyl-1,3,5-hexatriene for phospholipid quantitation.4 ,5 While comparative analysis of lung tissue and lavage fluid revealed the presence of large amounts of DPPC in lung tissue and lung lavage fluid,6 we did not find significant amounts of DPPC in either gastric mucosa or mucus.2 ,3 Instead, palmitoyloleoyl phosphatidylcholine (POPC) and palmitoyllinoleoyl phosphatidylcholine (PLPC) were abundant in gastric mucosa and were selectively increased in gastric mucus. These results were confirmed recently using electrospray ionisation mass spectrometric analysis of lipid extracts from gastric samples (unpublished data).
Identification of the effective absence of DPPC in gastric mucus has far reaching consequences for our understanding of the mechanism underlying the protection of the gastric mucosal surface by hydrophobic components, in many respects simplifying the concepts involved. The function of DPPC in pulmonary surfactant is dependent on its high gel to sol phase transition temperature (41°C) and consequently, DPPC is a solid material at body temperature. Pulmonary surfactant contains specialised unsaturated phosphatidylglycerols and specific apoprotein components designed to facilitate adsorption of DPPC to the air–liquid interface.7 These constraints will not apply to gastric surfactant, as this is composed of the more fluid molecules POPC and PLPC. This conjecture is in agreement with our finding that negligible amounts of phosphatidylglycerol were present in gastric mucus.2 Therefore, although we support Hills’ concepts of a phospholipid mediated hydrophobic barrier as the main factor in gastric mucosal protection, we disagree that this barrier is biochemically related to lung surfactant.
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Reply
Editor,—In responding to the letter by Bernhard and Postle it is important to emphasise agreement on the major issue that surface-active phospholipid (SAPL) protects the stomach wall from autodigestion, providing the gastric mucosal barrier to hydrated protons H(H2O)3 +. Protons are far too polarising to exist alone in an aqueous environment, the water of hydration being repelled by any hydrophobic domain. In my leading article great care was taken to use the term SAPL in all except the introductory remarks explaining arousal of my interest in mucosal protection on the basis of molecular similarities between cationic corrosion inhibitors and the pseudocationic dipalmitoyl phosphatidylcholine (DPPC) which, I thought at the time, might have reached the stomach by swallowing lung surfactant. Hence, it is incorrect to say that I claim DPPC to be “the main factor of gastric surfactant”. Bernhard and Postle are also incorrect in stating that we based our model on the analyses made some 20 years ago by Wassefet al,1-1 when we published our own analyses of surface scrapings taken along the whole gastrointestinal tract,1-2 displaying a range of phospholipid species not unlike that found in the lung—predominantly phosphatidylcholine (PC). Unfortunately, we did not have access to HPLC for fatty acid analysis at that time (15 years ago), and so I am quite prepared to accept their elegant and much later analyses displaying partially unsaturated PC. However, even unsaturated phospholipids display much surface activity,1-3 although their molecules may not pack together quite as neatly as their disaturated counterparts, as depicted in my model for barrier formation. The findings of Bernhard and Postle are consistent with our unpublished findings that, in rats, unsaturated exogenous PC offers comparable mucosal protection to saturated PC. Their point about the sol–gel transition of DPPC is only relevant to the lung where there is a fluid–air interface and even this is open to debate, but such controversies are better left to respiratory texts.1-4 The real point to remember is that it is the surface activity of the phospholipids, particularly the PCs, which permit binding of the surfactant to the tissue surface, enabling it to impart its highly desirable properties whether protection against corrosion in the stomach, lubrication in the joint,1-5 or any of a number of others based upon principles well established in the physical sciences.1-4