Modulation of the Plasma Kallikrein-Kinin System Proteins Performed by Heparan Sulfate Proteoglycans

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.

Bradykinin receptor in immune-mediated renal tubular injury in trichloroethylene-sensitized mice: Impact on NF-κB signaling pathway

“…In a previous study, it was found that TCE exposure resulted in kallikrein-kinin system (KKS) activation, including that of bradykinin (BK) and the bradykinin receptor (B1R/B2R). Human plasma KKS proteins are related to inflammatory responses and immune disease through BK (Motta and Tersariol 2017). BK is released from kininogen by kallikrein, and metabolized rapidly to Des-Arg-BK (DABK) by kininase (Sang et al 2016).…”

Differential processing of high‐molecular‐weight kininogen during normal pregnancy

“…FXI releases a large D5 fragment, Arg428‐Lys520 . Recently studied HK‐interacting proteases include: MASP‐1 and MASP‐2 (lectin pathway of complement activation), neutrophil elastase (increased in PE), FXII (increased in response to estrogen and implicated in recurrent pregnancy loss), tissue kallikrein, plasmin, and calpains . Human mast cell tryptase was shown to cleave multiple sites within the LC of HK .…”

“…Human mast cell tryptase was shown to cleave multiple sites within the LC of HK . Additionally, HK bound to ECs is internalized and fused to lysosomes, containing proteases such as cathepsins B and L …”

“…30 and implicated in recurrent pregnancy loss), tissue kallikrein, plasmin, and calpains. [36][37][38][39][40] Human mast cell tryptase was shown to cleave multiple sites within the LC of HK. 41 Additionally, HK bound to ECs is internalized and fused to lysosomes, containing proteases such as cathepsins B and L. 40 PROSPER analysis predicted proteolysis by cathepsin K, MMP-9, and MMP-3, which have been implicated in normal placentation, trophoblast invasion, and PE.…”

“…[36][37][38][39][40] Human mast cell tryptase was shown to cleave multiple sites within the LC of HK. 41 Additionally, HK bound to ECs is internalized and fused to lysosomes, containing proteases such as cathepsins B and L. 40 PROSPER analysis predicted proteolysis by cathepsin K, MMP-9, and MMP-3, which have been implicated in normal placentation, trophoblast invasion, and PE. [42][43][44][45] However, this analysis is limited due to PROSPER's exclusion of many known HK-interacting proteases from its database.…”