Cellular expression of plasma prekallikrein in human tissues

Abstract

Plasma prekallikrein (PPK) is synthesised in hepatocytes and secreted into the blood, where it participates in the surface-dependent activation of blood coagulation, fibrinolysis, kinin generation and inflammation. Recently we demonstrated by quantitative RT-PCR that the human PPK gene is transcribed not only in the liver, but also in various non-hepatic human tissues at significant levels. However, up to now no reliable information is available concerning protein synthesis in the corresponding human tissues. Here we demonstrate by immunohistochemical studies that PPK or plasma kallikrein (PK) is localised in cells of different embryologically derived human tissues. In the human nephron, single cells of the distal tubules stained intensely, while the cytoplasm of cells forming proximal tubules and collecting ducts stained uniformly. PPK/PK was localised in hepatic epithelial cells of the liver, in cells of the pancreatic islet of Langerhans, in the interstitial Leydig cells of the testes, in the follicular and thecal granulosa cells of the ovary, and in the parotid gland, oesophagus, skin, respiratory tract, prostate and breast. We conclude that the cellular localisation of PPK/PK in multiple different progenitorderived cells indicates specific cellular functions of this enzyme, in addition to its known function in the blood.

Murine prolylcarboxypeptidase depletion induces vascular dysfunction with hypertension and faster arterial thrombosis

“…In addition, intracellular kallikrein/kinin and renin-angiotensin systems have been described, which also may be contributory to endothelial cell function in PRCP gt/gt mice. 34,35 The 60% normal plasma factor XII levels seen in the gene-trap mice are probably of no significance. Although epidemiologic studies suggest that reduced plasma factor XII levels are associated with myocardial infarction, mice severely deficient in factor XII are protected from thrombosis and plasma levels of factor XII of only 10% to 15% in humans are sufficient to have normal blood coagulation times.…”

Prostatic trypsin-like kallikrein-related peptidases (KLKs) and other prostate-expressed tryptic proteinases as regulators of signalling via proteinase-activated receptors (PARs)

“…These include secreted enzymes, such as trypsin I, II (Paju et al, 2000;Bjartell et al, 2005) and IV (Takeuchi et al, 1999;Cottrell et al, 2004); other more complex secreted serine proteinases, containing modular nonproteolytic domains, such as factor XIIa (Takeuchi et al, 1999), plasma kallikrein (Neth et al, 2001;Fink et al, 2007), urokinase (also known as urinary plasminogen activator, uPA; Gavrilov et al, 2001;Riddick et al, 2005;Usher et al, 2005) and protein C (He et al, 1995;Takeuchi et al, 1999); the multi-serine proteinase domain containing enzymes polyserase-2 and -3 (Cal et al, 2005(Cal et al, , 2006; the glycosyl-phosphatidylinositol membraneanchored serine proteinase prostasin (Chen et al, 2001); as well as nine members of the type II transmembrane serine proteinase (TTSP) sub-family (Hooper et al, 2001;Netzel-Arnett et al, 2003) including hepsin, enteropeptidase (Cottrell et al, 2004), matriptase/MT-SP1 (Saleem et al, 2006), TMPRSS2 (Lin et al, 1999), TMPRSS3 (Scott et al, 2001), TMPRSS13 (Kim et al, 2001), human airway trypsin-like proteinase (HAT) (Hahner et al, 2005), DESC1 (Lang and Schuller, 2001) and the multi-catalytic domain TTSP polyserase-1 (Okumura et al, 2006). It is also interesting to note the co-expression in prostatederived cell lines of trypsinogen I, II and IV and the in vivo Brought to you by | University of Queensland -UQ Library Authenticated Download Date | 9/14/15 3:38 AM activator of these enzymes, the TTSP enteropeptidase (Light and Janska, 1989;Kitamoto et al, 1994).…”

Inhibition of carrageenan-induced expression of tissue and plasma prekallikreins mRNA by low level laser therapy in a rat paw edema model

“…Plasma prekallikrein (PPK) is synthesized by the hepatocytes and secreted into the bloodstream, where it participates in the surface-dependent activation of blood coagulation, fibrinolysis, kinin generation and inflammation. Human PPK gene is transcribed not only in the liver, but also in various nonhepatic human tissues at significant levels 9 . Carrageenan injection is a widely model used to induce acute inflammatory response in experimental animals that induces the release of different inflammatory mediators, such as histamine, bradykinin, prostaglandins and superoxide anions 10 .…”