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

J Della Vergiliana, Nithiananthan Asokananthan, G Stewart

    Research output: Contribution to journalArticleResearchpeer-review

    Abstract

    Activation of the tissue kallikrein-kinin system (KKS) plays a major inflammatory role in the lung, but the contribution of the plasma KKS remains unclear. Plasma KKS involves assembly and activation of high molecular weight kininogen (HK) and plasma prekallikrein (PPK) on cell surfaces, resulting in the liberation of the inflammatory peptide, bradykinin (BK), from HK by plasma kallikrein (PK). To this end, we determined the possible contribution of plasma KKS in BK formation using airway epithelium. The HK binding proteins, urokinase plasminogen activator receptor, cytokeratin 1 and gC1qR, were expressed on transformed A549 and BEAS-2B cell lines, as well as on normal lung tissue, but Mac-1 was absent. A549 cells bound FITC-labelled HK, which was only partially inhibited by a combination of antibodies to the HK binding proteins. HK-PPK complex activation on the transformed epithelial cell lines, as well as primary epithelial cells, resulted in PK formation and liberation of BK. HK-PPK activation was inhibited by cysteine, BK and protamine, and by novobiocin, a heat shock protein 90 (HSP90) inhibitor. In summary, lung epithelial cells support the assembly and activation of the plasma KKS by a mechanism dependent on HSP90, and could contribute to KKS-mediated inflammation in lung disease.
    Original languageEnglish
    Pages (from-to)1067-1077
    Number of pages11
    JournalBiological Chemistry
    Volume391
    Issue number9
    Early online date11 Jun 2010
    DOIs
    Publication statusPublished - 1 Sep 2010

    Fingerprint

    Plasma Kallikrein
    Kallikrein-Kinin System
    Kinins
    Epithelial Cells
    Chemical activation
    Bradykinin
    Prekallikrein
    Lung
    HSP90 Heat-Shock Proteins
    Plasmas
    Carrier Proteins
    High Molecular Weight Kininogens
    Urokinase Plasminogen Activator Receptors
    Novobiocin
    Tissue Kallikreins
    Pulmonary diseases
    Transformed Cell Line
    Kallikreins
    Protamines
    Fluorescein-5-isothiocyanate

    Cite this

    Della Vergiliana, J ; Asokananthan, Nithiananthan ; Stewart, G. / Activation of the plasma kallikrein-kinin system on human lung epithelial cells. In: Biological Chemistry. 2010 ; Vol. 391, No. 9. pp. 1067-1077.
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    abstract = "Activation of the tissue kallikrein-kinin system (KKS) plays a major inflammatory role in the lung, but the contribution of the plasma KKS remains unclear. Plasma KKS involves assembly and activation of high molecular weight kininogen (HK) and plasma prekallikrein (PPK) on cell surfaces, resulting in the liberation of the inflammatory peptide, bradykinin (BK), from HK by plasma kallikrein (PK). To this end, we determined the possible contribution of plasma KKS in BK formation using airway epithelium. The HK binding proteins, urokinase plasminogen activator receptor, cytokeratin 1 and gC1qR, were expressed on transformed A549 and BEAS-2B cell lines, as well as on normal lung tissue, but Mac-1 was absent. A549 cells bound FITC-labelled HK, which was only partially inhibited by a combination of antibodies to the HK binding proteins. HK-PPK complex activation on the transformed epithelial cell lines, as well as primary epithelial cells, resulted in PK formation and liberation of BK. HK-PPK activation was inhibited by cysteine, BK and protamine, and by novobiocin, a heat shock protein 90 (HSP90) inhibitor. In summary, lung epithelial cells support the assembly and activation of the plasma KKS by a mechanism dependent on HSP90, and could contribute to KKS-mediated inflammation in lung disease.",
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    Della Vergiliana, J, Asokananthan, N & Stewart, G 2010, 'Activation of the plasma kallikrein-kinin system on human lung epithelial cells', Biological Chemistry, vol. 391, no. 9, pp. 1067-1077. https://doi.org/10.1515/bc.2010.102

    Activation of the plasma kallikrein-kinin system on human lung epithelial cells. / Della Vergiliana, J; Asokananthan, Nithiananthan; Stewart, G.

    In: Biological Chemistry, Vol. 391, No. 9, 01.09.2010, p. 1067-1077.

    Research output: Contribution to journalArticleResearchpeer-review

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