Hydrolysis of kininogens by degranulated human neutrophils and analysis of bradykinin as chemotactic factor for cells isolated from peripheral blood

Figueroa, Carlos D.; Stuardo, Miguel; González, Carlos B.; Nualart, Francisco; Corthorn, Jenny; Borić, Mauricio P.; Bhoola, K. D.

doi:10.1016/s0162-3109(99)00092-2

Cited by 11 publications

(6 citation statements)

References 10 publications

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“…Previous studies have shown that stimulated neutrophils induced the generation of biologically active kinins from HK (36 -38), whereas nonstimulated neutrophils did not hydrolyze HK (39). Neutrophil-derived tissue kallikrein participated in kinin release as the reaction was blocked by antihuman urinary kallikrein but not by antineutrophil elastase Ab (36).…”

Section: Discussionmentioning

confidence: 91%

Neutrophil-Derived Proteinase 3 Induces Kallikrein-Independent Release of a Novel Vasoactive Kinin

Kahn¹,

Hellmark²,

Leeb-Lundberg

et al. 2009

The Journal of Immunology

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The kinin-forming pathway is activated on endothelial cells and neutrophils when high-molecular weight kininogen (HK) is cleaved by plasma kallikrein liberating bradykinin, a potent mediator of inflammation. Kinins are released during inflammatory conditions such as vasculitis, associated with neutrophil influx around blood vessels. Some patients with vasculitis have elevated plasma levels of neutrophil-derived proteinase 3 (PR3) and anti-PR3 Abs. This study investigated if neutrophil-derived PR3 could induce activation of the kinin pathway. PR3 incubated with HK, or a synthetic peptide derived from HK, induced breakdown and release of a novel tridecapeptide termed PR3-kinin, NH2-MKRPPGFSPFRSS-COOH, consisting of bradykinin with two additional amino acids on each terminus. The reaction was specific and inhibited by anti-PR3 and α1-antitrypsin. Recombinant wild-type PR3 incubated with HK induced HK breakdown, whereas mutated PR3, lacking enzymatic activity, did not. PR3-kinin bound to and activated human kinin B1 receptors, but did not bind to B2 receptors, expressed by transfected HEK293 cells in vitro. In human plasma PR3-kinin was further processed to the B2 receptor agonist bradykinin. PR3-kinin exerted a hypotensive effect in vivo through both B1 and B2 receptors as demonstrated using wild-type and B1 overexpressing rats as well as wild-type and B2 receptor knockout mice. Neutrophil extracts from vasculitis patients and healthy controls contained comparable amounts of PR3 and induced HK proteolysis, an effect that was abolished when PR3 was immunoadsorbed. Neutrophil-derived PR3 can proteolyze HK and liberate PR3-kinin, thereby initiating kallikrein-independent activation of the kinin pathway.

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Section: Discussionmentioning

confidence: 91%

Neutrophil-Derived Proteinase 3 Induces Kallikrein-Independent Release of a Novel Vasoactive Kinin

Kahn¹,

Hellmark²,

Leeb-Lundberg

et al. 2009

The Journal of Immunology

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“…In inflammation, the requirement for kinin precursors obviously increases. In previous studies, a disturbance of contact system equilibrium by proteinases from neutrophils at the inflammatory sites was suggested [29,30]. An additional supplementation of proteins involved in kinin generation at inflammatory site could diminish this effect.…”

Section: Discussionmentioning

confidence: 97%

Kininogen binding to the surfaces of macrophages

Barbasz

Guevara-Lora

Rapała‐Kozik

et al. 2008

International Immunopharmacology

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“…This migration could be markedly reduced by the appropriate inhibitors. Neutrophils bear kininogen (Figueroa et al, , 1999 Examples for normal, traumatised and diseased skin biopsies are depicted. Tissue kallikrein and tissue pro-kallikrein are both localised in basal mitotically active keratinocytes, as visualised by light microscopy using the peroxidase-antiperoxidase streptavidin-biotin conjugated method.…”

Section: Discussionmentioning

confidence: 99%

Visualisation of tissue kallikrein, kininogen and kinin receptors in human skin following trauma and in dermal diseases

Schremmer-Danninger¹,

Naidoo

Neuhof

et al. 2004

Biological Chemistry

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During dermal injury and inflammation the serine proteases kallikreins cleave endogenous, multifunctional substrates (kininogens) to form bradykinin and kallidin. The actions of kinins are mediated by preferential binding to constitutively expressed kinin-B2 receptors or inducible kinin-B1 receptors. A feature of the kinin-B1 receptors is that they show low levels of expression, but are distinctly upregulated following tissue injury and inflammation. Because recent evidence suggested that kinin-B1 receptors may perform a protective role during inflammation, we investigated the specific occurrence of the kallikrein-kinin components in skin biopsies obtained from normal skin, patients undergoing surgery, basalioma, lichenificated atopic eczema, and psoriasis. The tissue was immunolabelled in order to determine the localisation of tissue pro-kallikrein, kallikrein, kininogen and kinin receptors. The kinin components were visualised in normal, diseased and traumatised skin, except that no labelling was observed for kininogen in normal skin. Of the five types of tissue examined, upregulation of kinin-B1 receptors was observed only in skin biopsies obtained following surgery. In essence, the expression of

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Hydrolysis of kininogens by degranulated human neutrophils and analysis of bradykinin as chemotactic factor for cells isolated from peripheral blood

Cited by 11 publications

References 10 publications

Neutrophil-Derived Proteinase 3 Induces Kallikrein-Independent Release of a Novel Vasoactive Kinin

Neutrophil-Derived Proteinase 3 Induces Kallikrein-Independent Release of a Novel Vasoactive Kinin

Kininogen binding to the surfaces of macrophages

Visualisation of tissue kallikrein, kininogen and kinin receptors in human skin following trauma and in dermal diseases

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