High‐molecular‐weight kininogen is a binding protein for tissue prokallikrein

Raab, Armin; Kemme, Michael

doi:10.1016/s0014-5793(00)01141-8

Cited by 11 publications

(6 citation statements)

References 17 publications

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“…Other components of the kinin cascade, such as the kininogens and plasma prekallikrein, were also found to localize in the neutrophil cell membrane Henderson et al, 1994). Ligand blot assays suggest that pro-hK1 may attach to the cell membrane by interacting with high-molecular-weight kininogen, but not to its low-molecularweight form Raab and Kemme, 2000).…”

Section: Inflammation and Neutrophil Functionmentioning

confidence: 99%

10 Kallikrein-Kinin Cascade: Bioregulation by Human Tissue Kallikrein 1 (hK1, KLK1)

Figueroa¹,

Faußner²,

Bhoola³

2012

Kallikrein-Related Peptidases

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Section: Inflammation and Neutrophil Functionmentioning

confidence: 99%

10 Kallikrein-Kinin Cascade: Bioregulation by Human Tissue Kallikrein 1 (hK1, KLK1)

Figueroa¹,

Faußner²,

Bhoola³

2012

Kallikrein-Related Peptidases

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“…Similarly, Kemme et al [17] have shown that tissue prokallikrein localizes bound to the neutrophil surface in addition to the intracellular compartment. Ligand blot assays suggest that tissue prokallikrein may attach to the cell membrane also by interacting with H-kininogen [18]. In addition, binding experiments using purified cell membranes have shown that neutrophils display kinin-binding sites that have been characterized as B1 and B2 kinin receptor subtypes [19].…”

Section: Introductionmentioning

confidence: 99%

Stimulated human neutrophils form biologically active kinin peptides from high and low molecular weight kininogens

Stuardo

González

Nualart

et al. 2004

Journal of Leukocyte Biology

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Human neutrophils play a pivotal role in acute inflammation. However, their capacity to generate bioactive kinin peptides has not been established as yet. We have examined the ability of neutrophil enzymes to release biologically active kinins in vitro from purified human H- and L-kininogens. Neutrophils isolated from human blood were stimulated with f-Met-Leu-Phe, thrombin, or human immunoglobulin G adsorbed to silica particles. Supernatants were incubated with iodinated kininogens, and polyacrylamide gel electrophoresis analyzed aliquots taken after a range of incubation times. A time-course analysis demonstrated that supernatants from stimulated neutrophils caused a rapid hydrolysis of both substrates, resulting in an accumulation of fragments ranging from 20 to less than 10 kDa. Radioimmunoassay (RIA) revealed that all supernatants were able to generate kinins in vitro. High-performance liquid chromatography of the generated peptides indicated that they had a retention time similar to that of bradykinin and Met-Lys-bradykinin, clearly recognized as kinin peptides when the corresponding fractions were tested by RIA. The kinin-immunoreactive fractions produced lowering of blood pressure and a dramatic increase in venular permeability. Biological activity of the neutrophil-generated kinins was completely abolished by the B2 receptor antagonist HOE140, indicating that over the time-course of the experiments, only kinin B2 agonists appeared to have been generated and that cellular actions of these were mediated by kinin B2 receptors. Together, our results demonstrate that human neutrophil proteases can release kinins from both plasma kininogens, suggesting that these peptides may participate actively during acute inflammation.

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“…Nonspecific binding was subtracted from total HK binding, and binding affinity was calculated using Scatchard analysis. To determine the dependence of Ft/HK binding on the presence of zinc, 10 M ZnCl2 was added to each well along with biotinylated HK (38).…”

Section: Methodsmentioning

confidence: 99%

Cleavage of high-molecular-weight kininogen by elastase and tryptase is inhibited by ferritin

Coffman

Brown

Johnson

et al. 2008

American Journal of Physiology-Lung Cellular and Molecular Phys

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Ferritin is a protein principally known for its role in iron storage. We have previously shown that ferritin can bind high-molecular-weight kininogen (HK). Upon proteolytic cleavage by the protease kallikrein, HK releases the proinflammatory peptide bradykinin (BK) and other biologically active products, such as two-chain high-molecular-weight kininogen, HKa. At inflammatory sites, HK is oxidized, which renders it a poor substrate for kallikrein. However, oxidized HK remains a good substrate for elastase and tryptase, thereby providing an alternative cleavage mechanism for HK during inflammation. Here we report that ferritin can retard the cleavage of both native HK and oxidized HK by elastase and tryptase. Initial rates of cleavage were reduced 45-75% in the presence of ferritin. Ferritin is not a substrate for elastase or tryptase and does not interfere with the ability of either protease to digest a synthetic substrate, suggesting that ferritin may impede HK cleavage through direct interaction with HK. Immunoprecipitation and solid phase binding studies reveal that ferritin and HK bind directly with a Kd of 134 nM. To test whether ferritin regulates HK cleavage in vivo, we used THP-1 cells, a human monocyte/macrophage cell line that has been used to model pulmonary inflammatory cells. We observed that ferritin impedes the cleavage of HK by secretory proteases in stimulated macrophages. Furthermore, ferritin, HK, and elastase are all present in or on alveolar macrophages in a mouse model of pulmonary inflammation. Collectively, these results implicate ferritin in the modulation of HK cleavage at sites of inflammation.

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High‐molecular‐weight kininogen is a binding protein for tissue prokallikrein

Cited by 11 publications

References 17 publications

10 Kallikrein-Kinin Cascade: Bioregulation by Human Tissue Kallikrein 1 (hK1, KLK1)

10 Kallikrein-Kinin Cascade: Bioregulation by Human Tissue Kallikrein 1 (hK1, KLK1)

Stimulated human neutrophils form biologically active kinin peptides from high and low molecular weight kininogens

Cleavage of high-molecular-weight kininogen by elastase and tryptase is inhibited by ferritin

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