Abstract
Human plasma kallikrein-kinin system proteins are related to inflammation through bradykinin. In the proximity of its target cells, high molecular weight kininogen (H-kininogen) is the substrate of plasma kallikrein, which releases bradykinin from H-kininogen. Heparan sulfate proteoglycans (HSPGs) play a critical role in either recruiting kinin precursors from the plasma, or in the assembly of kallikrein-kinin system components on the cell surface. Furthermore, HSPGs mediate the endocytosis and activation of H-kininogen and plasma prekallikrein. In the presence of HSPGs (Chinese hamster ovary cell, CHO-K1, wild type cells) both heparin and heparan sulfate strongly inhibit the H-kininogen interaction with the cell membrane. H-kininogen is internalized in endosomal acidic vesicles in CHO-K1 but not in CHO-745 cells (mutant cells deficient in glycosaminoglycan biosynthesis). The endocytosis process is lipid raft-mediated and is dependent on caveolae. Both types of CHO cells do not internalize bradykinin-free H-kininogen. At pH 7.35, bradykinin is released from H-kininogen on the surface of CHO-745 cells only by serine proteases; however, in CHO-K1 cells either serine or cysteine proteases are found to be involved. The CHO-K1 cell lysate contains different kininogenases. Plasma prekallikrein endocytosis in CHO-K1 cells is independent of H-kininogen, and also prekallikrein is not internalized by CHO-745 cells. Plasma prekallikrein cleavage/activation is independent of glycosaminoglycans but plasma kallikrein formation is more specific on H-kininogen assembled on the cell surface through glycosaminoglycans. In this mini-review, the importance of HSPGs in the regulation of plasma kallikrein-kinin system proteins is shown.
Highlights
CELL SURFACE INTERACTIONThe interaction and activation of kallikrein-kinin system (KKS) on the cell surface of platelets, neutrophils, endothelial cells, and macrophages have been described (Colman, 2006; Schmaier and McCrae, 2007; Barbasz et al, 2008)
Reviewed by: Carlos Rocha Oliveira, Anhembi Morumbi University, Brazil Luciana Lopes Guimaraes, Universidade Santa Cecilia, Brazil
Plasma prekallikrein endocytosis in cell line from Chinese hamster ovary cells (CHO)-K1 cells is independent of H-kininogen, and prekallikrein is not internalized by CHO-745 cells
Summary
The interaction and activation of KKS on the cell surface of platelets, neutrophils, endothelial cells, and macrophages have been described (Colman, 2006; Schmaier and McCrae, 2007; Barbasz et al, 2008). The H-kininogen cleavage by KAL promotes conformational changes in BK-free H-kininogen and exposure of domain 5 (D5), which inhibits endothelial cell migration and proliferation, both of which play a role in angiogenesis (Guo and Colman, 2005). This potent anti-angiogenic activity occurs through tight-binding to cell surface tropomyosin which induces endothelial cell apoptosis (McCrae et al, 2005). The findings of the current research group show that cathepsin B has kininogenase activity at pH 6.3, which is improved in the absence of divalent cations (Zn2+, Mg2+, and Ca2+), at pH 7.35 cathepsin kininogenase activity is impaired suggesting that H-kininogen is a substrate for cathepsin B under pathophysiological conditions (Barros et al, 2004a)
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