It cannot be excluded that the interaction of PCI with the catalytically active light chain of EP is influenced by membrane anchoring of EP. However, the huge heavy chain lies in between the active center and the plasma membrane. This could hinder potential phospholipid-bridging of PCI and the light chain of EP. It is therefore not very likely that phospholipids involved in anchoring of EP could represent a bridge for bringing together PCI and EP. Several publications have shown that PCI mRNA is highly expressed in the pancreas, particularly in the exocrine part. We could show by Western blotting that PCI protein is present in human pancreas lysate. However, we were not able to show its presence in the exocrine part by immunohistochemistry on paraffin-embedded tissue sections. Activation of SJN 2511 trypsinogen is a crucial step in the pathogenesis of necrotizing pancreatitis. So far, it is not fully understood how trypsinogen is activated prematurely within the pancreas. Some authors believe that this activation might origin from reflux of EPcontaining duodenal fluid into the pancreatic duct. Though, this theory remains controversial and it is not clear if duodenopancreatic reflux occurs in vivo and, if it does, whether it is really able to damage the pancreas profoundly. However, if duodenopancreatic reflux occurs under some circumstances, inhibition of EP by PCI might have a protective effect. In addition, PCI could protect the pancreas from autodigestion by inhibiting trypsin and chymotrypsin. Polymorphisms of PSTI are associated with a higher incidence of pancreatitis, suggesting that this inhibitor may have a protective effect against this disease. Polymorphisms of PCI have been investigated with respect to male fertility. Further studies are needed to address the question if polymorphisms of PCI might also be associated with pancreatitis. PCI has also been identified in the epidermis, with increasing amounts in its more superficial layers. Desquamation of keratinocytes is controlled by several proteases and their inhibitors. An imbalance between them can lead to inflammatory skin diseases such as psoriasis. Since both, EP and PCI, are expressed in the upper epidermis, the interaction of EP and PCI might also be involved in the regulation of epidermal differentiation. The SI value of the PCI/EP-interaction is rather high, especially in the presence of heparin, suggesting that a significant amount of PCI is cleaved/inactivated by EP. The biological consequences of the PCI/EP-interaction may depend on the local : ratio. At a high : ratio, the inhibition of EP would be nearly complete leading to impaired activation of trypsinogen. Additionally, some active PCI would still be available to inhibit trypsin directly, further reducing its activity. At a low : ratio, the available PCI would not be sufficient to completely inhibit EP. Remaining active EP would still be able to SP600125 JNK inhibitor activate trypsinogen and to cleave PCI. For the digestive system, this could mean that in the pancreatic duct, any possibly present EP could be efficiently inhibited by PCI. In the duodenum, where EP is abundantly present, PCI would have only a minor effect on EP activity and would not significantly interfere with the activation of digestive proteases. In the epidermis, where EP is mainly localized in the superficial layers, any EP present in more basal layers would be efficiently inhibited by excess PCI. In more superficial layers, EP would be able to activate trypsinogen in significant amounts, so it can contribute to the desquamation process. Chondrosarcomas constitute a heterogeneous group of neoplasms accounting for 20% of bone malignancies, that have in common the production of cartilage-like matrix by the tumor cells.