Activation of the plasma kallikrein-kinin system on human lung epithelial cells

Vergiliana, Julius F. Varano della; Asokananthan, Nithiananthan; Stewart, Geoffrey A.

doi:10.1515/bc.2010.102

Cited by 7 publications

(4 citation statements)

References 64 publications

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“…Rabbit polyclonal anti‐A2, monoclonal anti‐S100‐A10, polyclonal anti‐Occludin, polyclonal anti‐Flotillin 1, and polyclonal anti‐uPA antibodies were from Abcam, Cambridge, MA (Chakraborty et al., 2012; Du et al., 2010; Yang et al., 2011). Mouse monoclonal anti‐uPAR and goat polyclonal anti‐CD71 were from R&D Systems Minneapolis, MN (Chakraborty et al., 2011; Vergiliana et al., 2010). Rabbit polyclonal anti‐uPAR and mouse anti‐rabbit conformation specific secondary antibodies linked to HRP were from Cell Signaling Technologies, Boston, MA.…”

Section: Methodsmentioning

confidence: 99%

Angiogenin interacts with the plasminogen activation system at the cell surface of breast cancer cells to regulate plasmin formation and cell migration

et al. 2014

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Angiogenin Breast cancerPlasminogen activation system Plasmin Cell migration A B S T R A C TAngiogenin (ANG), a 14-kDa pro-angiogenic secreted protein, has been shown to play a role in cell migration and tumor invasion, which involve proteolytic cleavage of plasminogen to generate plasmin. However, the mechanism by which ANG regulates plasmin formation and cell migration was not known. Our studies here detected elevated levels of secreted and cell surface-bound ANG in highly invasive metastatic breast cancer cells. ANG was also detected at very high levels in the tumor cells in infiltrating ductal carcinomas. By immunofluorescence and immunoprecipitation analysis, ANG was detected at the leading edges of the cell surfaces where it colocalized and interacted with members of the plasminogen activation system (PAS) such as annexin A2 (A2), calpactin (S100-A10) and urokinase plasminogen activator receptor (uPAR). Analysis of lipid raft (LR) and non-lipid raft (NLR) regions of the cell membranes showed the predominance of ANG, A2 and S100-A10 in the LR regions. In contrast, uPAR was detected predominantly in the NLR fractions, suggesting that ANG interacts with uPAR at the junctions of LR and NLR regions. ANG knockdown in T47D and MDA-MB-231 breast cancer cell lines did not affect the cellular expression of A2, S100-A10 and uPAR but decreased cell migration and plasmin formation. Neutralization of ANG with monoclonal antibodies similarly decreased the migration of MDA-MB-231 cells. In the presence of ANG, uPAR was observed to interact with uPA, which is necessary for plasmin formation. Conversely, in the absence of ANG, uPAR did not interact with uPA and FAK and Src kinases were observed to be dephosphorylated. Published by Elsevier B.V. All rights reserved.Abbreviations: ANG, angiogenin; A2, annexin A2; LR, lipid rafts; NLR, non-lipid rafts; PAS, plasminogen activation system; PAI, plasminogen activator inhibitor; uPA, urokinase plasminogen activator; uPAR, urokinase plasminogen activator receptor; S100-A10, calpactin S100-A10; VT, vitronectin.* Corresponding author. Tel.: þ1 847 578 8323. E-mail address: sujoy.dutta@rosalindfranklin.edu (S. Dutta).

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Section: Methodsmentioning

confidence: 99%

Angiogenin interacts with the plasminogen activation system at the cell surface of breast cancer cells to regulate plasmin formation and cell migration

et al. 2014

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“…Plasma kallikrein-kinin proteins have also been found on the surface and in the extracellular matrix of endothelial cells from line ECV304 [23], vascular smooth muscle cells [24], immortalized human EA.hy926 endothelial cells [25], lung epithelial cells [26] and endothelial cells from a line derived from rabbit aorta RAECs [27]. Little is known regarding the mechanisms of plasma prekallikrein interactions with cells.…”

Section: Introductionmentioning

confidence: 99%

The Involvement of Proteoglycans in the Human Plasma Prekallikrein Interaction with the Cell Surface

Veronez

Nascimento²,

Melo

et al. 2014

PLoS ONE

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IntroductionThe aim of this work was to evaluate the role of human plasma prekallikrein assembly and processing in cells and to determine whether proteoglycans, along with high molecular weight kininogen (H-kininogen), influence this interaction.MethodsWe used the endothelial cell line ECV304 and the epithelial cell lines CHO-K1 (wild type) and CHO-745 (deficient in proteoglycans). Prekallikrein endocytosis was studied using confocal microscopy, and prekallikrein cleavage/activation was determined by immunoblotting using an antibody directed to the prekallikrein sequence C364TTKTSTR371 and an antibody directed to the entire H-kininogen molecule.ResultsAt 37°C, prekallikrein endocytosis was assessed in the absence and presence of exogenously applied H-kininogen and found to be 1,418.4±0.010 and 1,070.3±0.001 pixels/cell, respectively, for ECV304 and 1,319.1±0.003 and 631.3±0.001 pixels/cell, respectively, for CHO-K1. No prekallikrein internalization was observed in CHO-745 in either condition. Prekallikrein colocalized with LysoTracker in the absence and presence of exogenous H-kininogen at levels of 76.0% and 88.5%, respectively, for ECV304 and at levels of 40.7% and 57.0%, respectively, for CHO-K1. After assembly on the cell surface, a plasma kallikrein fragment of 53 kDa was predominant in the incubation buffer of all the cell lines studied, indicating specific proteolysis; plasma kallikrein fragments of 48–44 kDa and 34–32 kDa were also detected in the incubation buffer, indicating non-specific cleavage. Bradykinin free H-kininogen internalization was not detected in CHO-K1 or CHO-745 cells at 37°C.ConclusionThe prekallikrein interaction with the cell surface is temperature-dependent and independent of exogenously applied H-kininogen, which results in prekallikrein endocytosis promoted by proteoglycans. Prekallikrein proteolysis/activation is influenced by H-kininogen/glycosaminoglycans assembly and controls plasma kallikrein activity.

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“…This binding has been described on endothelial cells [2e4,6], neutrophils [7], platelets [8], astrocytes [9], vascular smooth muscle cells [10] and macrophages [11]. Just out of interest, plasma kallikrein-kinin system activation (including HK binding) has also been described in a range of epithelial cells (e.g., lung, gut and prostate epithelium) [12]. On the endothelial cell surface, some proteins have been found to contain HK binding sites; these include urokinase plasminogen activator receptor (uPAR), cytokeratin 1 and receptor for the globular heads of complement component C1q (gC1qR) [13].…”

Section: Introductionmentioning

confidence: 99%

Heparin affects the interaction of kininogen on endothelial cells

et al. 2011

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In the plasma kallikrein-kinin system, it has been shown that when plasma prekallikrein (PK) and high molecular weight kininogen (HK) assemble on endothelial cells, plasma kallikrein (huPK) becomes available to cleave HK, releasing bradykinin, a potent mediator of the inflammatory response. Because the formation of soluble glycosaminoglycans occurs concomitantly during the inflammatory processes, the effect of these polysaccharides on the interaction of HK on the cell surface or extracellular matrix (ECM) of two endothelial cell lines (ECV304 and RAEC) was investigated. In the presence of Zn(+2), HK binding to the surface or ECM of RAEC was abolished by heparin; reduced by heparan sulfate, keratan sulfate, chondroitin 4-sulfate or dermatan sulfate; and not affected by chondroitin 6-sulfate. By contrast, only heparin reduced HK binding to the ECV304 cell surface or ECM. Using heparin-correlated molecules such as low molecular weight dextran sulfate, low molecular weight heparin and N-desulfated heparin, we suggest that these effects were mainly dependent on the charge density and on the N-sulfated glucosamine present in heparin. Surprisingly, PK binding to cell- or ECM-bound-HK and PK activation was not modified by heparin. However, the hydrolysis of HK by huPK, releasing BK in the fluid phase, was augmented by this glycosaminoglycan in the presence of Zn(2+). Thus, a functional dichotomy exists in which soluble glycosaminoglycans may possibly either increase or decrease the formation of BK. In conclusion, glycosaminoglycans that accumulated in inflammatory fluids or used as a therapeutic drug (e.g., heparin) could act as pro- or anti-inflammatory mediators depending on different factors within the cell environment.

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Activation of the plasma kallikrein-kinin system on human lung epithelial cells

Cited by 7 publications

References 64 publications

Angiogenin interacts with the plasminogen activation system at the cell surface of breast cancer cells to regulate plasmin formation and cell migration

Angiogenin interacts with the plasminogen activation system at the cell surface of breast cancer cells to regulate plasmin formation and cell migration

The Involvement of Proteoglycans in the Human Plasma Prekallikrein Interaction with the Cell Surface

Heparin affects the interaction of kininogen on endothelial cells

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