Kininogen binding to the surfaces of macrophages

Barbasz, Anna; Guevara-Lora, Ibeth; Rapała‐Kozik, Maria; Kozik, Andrzej

doi:10.1016/j.intimp.2007.08.002

Cited by 30 publications

(21 citation statements)

References 31 publications

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“…Consistent with that hypothesis, the yield of kinin production from HK was an order of magnitude lower than that from LK, additionally suggesting some shielding of the kinin-containing domain D4 by the light chain against SAP2 action. According to a generally accepted model, the two forms of human kininogens play different roles at local infl ammatory foci, LK being the preferable substrate for kinin production in the fl uid phase by tissue kallikrein (Joseph and Kaplan , 2005 ) and HK being a substrate for the cell surface-localized kinin release, primarily by plasma kallikrein (Reddigari et al , 1995 ;Barbasz et al , 2008 ;Barbasz and Kozik , 2009 ). In the context of candidiasis, our present fi ndings suggest that the two mechanisms of the fungal infection-associated upregulation of kinin-forming systems, i.e., the pathogen cell wall-dependent contact system activation vs. the release of kinins from kininogens by SAPs, have distinct signifi cances.…”

Section: Discussionmentioning

confidence: 99%

Extracellular aspartic protease SAP2 of Candida albicans yeast cleaves human kininogens and releases proinflammatory peptides, Met-Lys-bradykinin and des-Arg⁹-Met-Lys-bradykinin

Bras

Bocheńska

Rapała‐Kozik

et al. 2012

Biological Chemistry

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Bradykinin-related peptides, universal mediators of infl ammation collectively referred to as the kinins, are often produced in excessive amounts during microbial infections. We have recently shown that the yeast Candida albicans , the major fungal pathogen to humans, can exploit two mechanisms to enhance kinin levels at the sites of candidial infection, one depending on adsorption and activation of the endogenous kinin-generating system of the host on the fungal cell wall and the other relying on cleavage of kinin precursors, the kininogens, by pathogen-secreted proteases. This work aimed at assigning this kininogenase activity to the major secreted aspartic protease of C. albicans (SAP2). The purifi ed SAP2 was shown to cleave human kininogens, preferably the low molecular mass form (LK) and optimally in an acidic environment (pH 3.5 -4.0), and to produce two kinins, Met-Lys-bradykinin and its derivative, [Hydroxyproline 3 ]-Met-Lys-bradykinin, both of which are capable of interacting with cellular bradykinin receptors of the B2 subtype. Additionally, albeit with a lower yield, des-Arg 9 -Met-Lysbradykinin, an effective agonist of B1-subtype receptors, was released. The pathophysiological potential of these kinins and des-Arg-kinin was also proven by presenting their ability to stimulate human promonocytic cells U937 to release proinfl ammatory interleukin 1 β (IL-1 β ) and IL-6.

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Section: Discussionmentioning

confidence: 99%

Extracellular aspartic protease SAP2 of Candida albicans yeast cleaves human kininogens and releases proinflammatory peptides, Met-Lys-bradykinin and des-Arg⁹-Met-Lys-bradykinin

Bras

Bocheńska

Rapała‐Kozik

et al. 2012

Biological Chemistry

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“…A major pathway for kinin production at these locations depends on the adsorption (the contact system) and activation of the Hageman factor (FXII) on the surfaces of endothelium and other host cells (5,6,23,34,56). Within a ternary complex assembled on the cell surface, the activated FXII converts plasma prekallikrein (PK) into the active enzyme which subsequently releases bradykinin from high-molecular-mass kininogen (HK).…”

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confidence: 99%

Adsorption of Components of the Plasma Kinin-Forming System on the Surface ofPorphyromonas gingivalisInvolves Gingipains as the Major Docking Platforms

et al. 2011

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Enhanced production of proinflammatory bradykinin-related peptides, the kinins, has been suggested to contribute to the pathogenesis of periodontitis, a common inflammatory disease of human gingival tissues. In this report, we describe a plausible mechanism of activation of the kinin-generating system, also known as the contact system or kininogen-kallikrein-kinin system, by the adsorption of its plasma-derived components such as high-molecular-mass kininogen (HK), prekallikrein (PK), and Hageman factor (FXII) to the cell surface of periodontal pathogen Porphyromonas gingivalis. The adsorption characteristics of mutant strains deficient in selected proteins of the cell envelope suggested that the surface-associated cysteine proteinases, gingipains, bearing hemagglutinin/adhesin domains (RgpA and Kgp) serve as the major platforms for HK and FXII adhesion. These interactions were confirmed by direct binding tests using microplate-immobilized gingipains and biotinylated contact factors. Other bacterial cell surface components such as fimbriae and lipopolysaccharide were also found to contribute to the binding of contact factors, particularly PK. Analysis of kinin release in plasma upon contact with P. gingivalis showed that the bacterial surface-dependent mechanism is complementary to the previously described kinin generation system dependent on HK and PK proteolytic activation by the gingipains. We also found that several P. gingivalis clinical isolates differed in the relative significance of these two mechanisms of kinin production. Taken together, these data show the importance of this specific type of bacterial surface-host homeostatic system interaction in periodontal infections.

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“…Second, Sugi et al found that the antibody purified from plasma of patients with anti-phospholipid syndrome recognizes HK in the presence of PS (38), suggesting that plasma HK forms a complex with PS in vivo which becomes immunogenic. Third, we and others have previously shown that HK binds to a variety of cells including leukocytes and endothelial cells via uPAR (30–31, 39–41). Fourth, our recent study using surface plasmon resonance has shown that compared to HK, the affinity of suPAR for HKa was 53-fold tighter (42).…”

Section: Discussionmentioning

confidence: 85%

High Molecular Weight Kininogen Binds Phosphatidylserine and Opsonizes Urokinase Plasminogen Activator Receptor–Mediated Efferocytosis

Yang

Dai

Xie

et al. 2014

The Journal of Immunology

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Summary Phagocytosis of apoptotic cells (efferocytosis) is essential for regulation of immune responses and tissue homeostasis, and is mediated by phagocytic receptors. In this study we found that urokinase plasminogen activator receptor (uPAR) plays an important role in internalization of apoptotic cells, and also characterized the underlying mechanisms. In a flow cytometry-based phagocytic assay, uPAR-deficient (uPAR−/−) macrophages displayed significant defect in internalization but not tethering of apoptotic cells. When uPAR−/− mice were challenged with apoptotic cells, they exhibited pronounced splenomegaly resulting from accumulation of abundant apoptotic cells in spleen. Overexpression of uPAR in HEK-293 cells enhanced efferocytosis, which was inhibited by annexin V and phosphatidylserine (PS) liposome, suggesting that uPAR-mediated efferocytosis is dependent on PS. In serum lacking high-molecular-weight kininogen (HK), a uPAR ligand, uPAR-mediated efferocytosis was significantly attenuated, which was rescued by replenishment of HK. As detected by flow cytometry, HK selectively bound to apoptotic cells, but not viable cells. In purified systems, HK was specifically associated with PS liposome. HK binding to apoptotic cells induced its rapid cleavage to two-chain HKa and bradykinin. Both heavy chain and light chain of HKa were associated with PS liposome and apoptotic cells. HKa has higher binding affinity than HK to uPAR. Overexpression of Rac1/N17 cDNA inhibited uPAR-mediated efferocytosis. HK plus PS liposome stimulated a complex formation of CrkII with p130Cas and Dock-180, and Rac1 activation in uPAR-293 cells, but not in control HEK-293 cells. Thus, uPAR mediates efferocytosis through HK interaction with PS on apoptotic cells and activation of Rac1 pathway.

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Kininogen binding to the surfaces of macrophages

Cited by 30 publications

References 31 publications

Extracellular aspartic protease SAP2 of Candida albicans yeast cleaves human kininogens and releases proinflammatory peptides, Met-Lys-bradykinin and des-Arg⁹-Met-Lys-bradykinin

Extracellular aspartic protease SAP2 of Candida albicans yeast cleaves human kininogens and releases proinflammatory peptides, Met-Lys-bradykinin and des-Arg⁹-Met-Lys-bradykinin

Adsorption of Components of the Plasma Kinin-Forming System on the Surface ofPorphyromonas gingivalisInvolves Gingipains as the Major Docking Platforms

High Molecular Weight Kininogen Binds Phosphatidylserine and Opsonizes Urokinase Plasminogen Activator Receptor–Mediated Efferocytosis

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Kininogen binding to the surfaces of macrophages

Cited by 30 publications

References 31 publications

Extracellular aspartic protease SAP2 of Candida albicans yeast cleaves human kininogens and releases proinflammatory peptides, Met-Lys-bradykinin and des-Arg9-Met-Lys-bradykinin

Extracellular aspartic protease SAP2 of Candida albicans yeast cleaves human kininogens and releases proinflammatory peptides, Met-Lys-bradykinin and des-Arg9-Met-Lys-bradykinin

Adsorption of Components of the Plasma Kinin-Forming System on the Surface ofPorphyromonas gingivalisInvolves Gingipains as the Major Docking Platforms

High Molecular Weight Kininogen Binds Phosphatidylserine and Opsonizes Urokinase Plasminogen Activator Receptor–Mediated Efferocytosis

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Extracellular aspartic protease SAP2 of Candida albicans yeast cleaves human kininogens and releases proinflammatory peptides, Met-Lys-bradykinin and des-Arg⁹-Met-Lys-bradykinin

Extracellular aspartic protease SAP2 of Candida albicans yeast cleaves human kininogens and releases proinflammatory peptides, Met-Lys-bradykinin and des-Arg⁹-Met-Lys-bradykinin