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Editor,—Phospholipase A2(PLA2) is an enzyme that cleaves fatty acids from phospholipids, leading to the generation of inflammatory eicosanoids.1 The group II isoenzyme of phospholipase A2 (PLA2-II) is raised in peripheral blood during various inflammatory states.2 PLA2 is induced in vitro and in vivo by the classic acute phase cytokine interleukin 6.3 4 Therefore PLA2-II can be regarded as an acute phase protein. With great interest we read the well designed study of Furue et al(Gut1997;41:826–31) who could clearly show that most PLA2 activity during sodium deoxycholate induced acute pancreatitis in rats is due to the group II isoenzyme. Furue and colleagues suggested that the liver is the main source of this enzyme in their experiments because Nevalainen and coworkers5 and Crowl and coworkers3 described PLA2-II activity in human hepatocytes. We agree with the suggestion of Furue et al that PLA2-II is produced in human hepatocytes like classic acute phase proteins. This was also demonstrated by our group,6but we think that the extrapolation of these findings from human tissue to animal experiments, as done by Furue et al, requires some clarification. Hatch et alwere able to show that liver macrophages and not hepatocytes were the main source of PLA2-II in rats during endotoxin induced acute phase reaction.7 As a consequence, liver macrophages but not hepatocytes could also be the main source of PLA2-II in the animal experiments presented by Furue and collaborators. Therefore an alternative pathogenetic mechanism leading to liver damage in experimental induced acute pancreatitis should be taken into account. Our alternative pathogenetic sequence is that PLA2-II released by liver macrophages attacks adjacent already damaged liver tissue, thus leading to complete destruction of hepatocytes with subsequent release of aminotransferases into the circulation, as shown by Furue et al. In conclusion, we agree that PLA2-II could be an important mediator of liver failure in acute pancreatitis, but alternative pathomechanisms resulting from different production sites should be discussed.
Editor,—We thank Drs Bertsch and Fischer for their interest in our paper. As group II PLA2(PLA2-II) is known to be produced from a variety of cells upon stimulation with various stimuli, it is still difficult to ascertain the main source of increased levels of this enzyme in the circulation both in animal models of inflammation and in human patients.1-1 1-2 As Bertsch and Fischer comment, we have to be careful about transferring findings from human tissue to animal experiments. Also of note is that liver macrophages (Kupffer cells) and not hepatocytes could be the main source of PLA2-II in our experiments on acute pancreatitis in rats. However, in contrast to the findings by Hatch and colleagues1-3 rat cultured hepatocytes can produce PLA2-II upon stimulation via chemical hypoxic injury,1-4 suggesting that the production of PLA2-II depends on both the type of cell and also the type of stimulus used. So we still think that hepatocytes are the main source of PLA2-II in our experiments. In addition, vascular smooth muscle cells could also be a potential source of PLA2-II as reported by Nakano and Arita1-5 who found high levels of PLA2-II transcripts in aorta of endotoxaemic rats. Very recently high levels of PLA2-II protein and overexpression of its mRNA in vascular tissue were also found in rat adjuvant arthritis.1-6 Therefore, the possible sources of PLA2-II in our rat acute pancreatitis could be hepatocytes, Kupffer cells and smooth muscle cells, and this enzyme from different type of cells would work in concert to damage liver tissue. Of course, the immunohistochemical study to identify the cellular source of PLA2-II in our experiments should be performed.
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