Formation of Bradykinin: A Major Contributor to the Innate Inflammatory Response

Joseph, Kusumam; Kaplan, Allen P.

doi:10.1016/s0065-2776(04)86005-x

Cited by 123 publications

(93 citation statements)

References 222 publications

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“…Furthermore, as a vasoactive peptide, BK can cause venular dilatation and constriction of coronary arteries, bronchi, and gastrointestinal smooth muscles. 13 Most of these processes are regulated via cytokines such as IL-6 and IL-8 or TNF-alpha, making BK an important player during inflammatory processes. 13 Because BK has many functions, it is linked to several disorders such as hereditary angioedema, allergic reactions including asthma, high blood pressure, but also rheumatoid arthritis, pancreatitis, and Alzheimer's disease.…”

Section: Contact Activationmentioning

confidence: 99%

“…13 Most of these processes are regulated via cytokines such as IL-6 and IL-8 or TNF-alpha, making BK an important player during inflammatory processes. 13 Because BK has many functions, it is linked to several disorders such as hereditary angioedema, allergic reactions including asthma, high blood pressure, but also rheumatoid arthritis, pancreatitis, and Alzheimer's disease. 13 BK can be further cleaved after which the various kinins are involved in both acute and chronic inflammatory responses.…”

Section: Contact Activationmentioning

confidence: 99%

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Recent insights into the role of the contact pathway in thrombo-inflammatory disorders

Montfoort

Meijers

2014

Hematology

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The contact pathway of coagulation consists of the proteins factor XI, factor XII, prekallikrein, and high-molecularweight kininogen. Activation of the contact system leads to procoagulant and proinflammatory reactions. The contact system is essential for surface-initiated coagulation, as exemplified by aPTT, but there is probably no role for the contact system in initiating physiologic in vivo coagulation. However, over the last few years, there has been renewed interest, especially because of experimental evidence suggesting that the contact system contributes to thrombosis. Knockout mice deficient in one of the contact proteins were protected against artificially induced thrombosis. Furthermore, inhibiting agents such as monoclonal antibodies, antisense oligonucleotides, and small molecules were found to prevent thrombosis in rodents and primates in both venous and arterial vascular beds. Although it remains to be established whether targeting the contact system will be effective in humans and which of the contact factors is the best target for anticoagulation, it would constitute a promising approach for future effective and safe antithrombotic therapy. Learning Objectives• To understand that the contact system consists of 4 proteins: factor XI, factor XII, PK, and HK • To understand that deficiency of factor XII, PK, or HK is not associated with a bleeding tendency in humans • To understand that targeting the contact system is an effective method to prevent thrombosis in mice •

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Section: Contact Activationmentioning

confidence: 99%

Section: Contact Activationmentioning

confidence: 99%

Recent insights into the role of the contact pathway in thrombo-inflammatory disorders

Montfoort

Meijers

2014

Hematology

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“…Because bradykinin is one of the most potent endogenous vasoactive peptides 37 and previous studies have shown that S. aureus can induce the release of bradykinin by activating the contact system, also known as the intrinsic pathway of coagulation, 38 we hypothesized that activation of the contact system in the A/J and the concomitant release of bradykinin may play an impor- tant role in the induction of the observed vascular leakage. To test this hypothesis, we determined the extent of contact activation in S. aureus-infected A/J and C57BL/6 mice by measuring the activated partial thromboplastin time (aPTT).…”

Section: Activation Of the Contact System In A/j But Not In C57bl/6 Mmentioning

confidence: 99%

Immunological Mechanisms Underlying the Genetic Predisposition to Severe Staphylococcus aureus Infection in the Mouse Model

Köckritz-Blickwede

Rohde

Oehmcke

et al. 2008

The American Journal of Pathology

119

120

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Host genetic variations play a significant role in conferring predisposition to infection. In this study, we examined the immune mechanisms underlying the host genetic predisposition to severe Staphylococcus aureus infection in different mouse strains. Whereas C57BL/6 mice were the most resistant in terms of control of bacterial growth and survival, A/J, DBA/2, and BALB/c mice were highly susceptible and succumbed to infection shortly after bacterial inoculation. Other strains (C3H/HeN, CBA, and C57BL/10) exhibited intermediate susceptibility levels. Susceptibility of mice to S. aureus was associated with an inability to limit bacterial growth in the kidneys and development of pathology. Resistance to S. aureus in C57BL/6 mice was dependent on innate immune mechanisms because Rag2-IL2R␥ ؊/؊ C57BL/6 mice, which are deficient in B, T, and NK cells, were also resistant to infection. Indeed, neutrophil depletion or inhibition of neutrophil recruitment rendered C57BL/6 mice completely susceptible to S. aureus, indicating that neutrophils are essential for the observed resistance. Although neutrophil function is not inhibited in A/J mice, expression of neutrophil chemoattractants KC and MIP-2 peaked earlier in the kidneys of C57BL/6 mice than in A/J mice, indicating that a delay in neutrophil recruitment to the site of infection may underlie the increased susceptibility of A/J mice to S.

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“…Angemeldet | 129.187.254.47 Heruntergeladen am | 07.11.13 15:00 host cells (Joseph and Kaplan, 2005;Barbasz et al, 2008;Barbasz and Kozik, 2009) and could play a role in maintaining the host-pathogen equilibrium or in the pathogenesis of mild superficial candidial infections. Severe fungal infections of inner organs, candidemia or Candida-dependent sepsis are likely to involve more drastic kinin-generating factors such as proteinases secreted by Candida cells, particularly if they can act directly on kinin precursors, the kininogens.…”

Section: Bereitgestellt Von | Universitaetsbibliothek Der Lmu Muenchenmentioning

confidence: 99%

Degradation of human kininogens with the release of kinin peptides by extracellular proteinases of Candida spp.

Rapała‐Kozik

Karkowska‐Kuleta

Ryzanowska

et al. 2010

Biological Chemistry

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The secretion of proteolytic enzymes by pathogenic microorganisms is one of the most successful strategies used by pathogens to colonize and infect the host organism. The extracellular microbial proteinases can seriously deregulate the homeostatic proteolytic cascades of the host, including the kinin-forming system, repeatedly reported to be activated during bacterial infection. The current study assigns a kininreleasing activity to secreted proteinases of Candida spp. yeasts, the major fungal pathogens of humans. Of several Candida species studied, C. parapsilosis and C. albicans in their invasive filamentous forms are shown to produce proteinases which most effectively degrade proteinaceous kinin precursors, the kininogens. These enzymes, classified as aspartyl proteinases, have the highest kininogen-degrading activity at low pH (approx. 3.5), but the associated production of bradykinin-related peptides from a small fraction of kininogen molecules is optimal at neutral pH (6.5). The peptides effectively interact with cellular B2-type kinin receptors. Moreover, kinin-related peptides capable of interacting with inflammation-induced B1-type receptors are also formed, but with a reversed pH dependence. The presented variability of the potential extracellular kinin production by secreted aspartyl proteinases of Candida spp. is consistent with the known adaptability of these opportunistic pathogens to different niches in the host organism.

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Formation of Bradykinin: A Major Contributor to the Innate Inflammatory Response

Cited by 123 publications

References 222 publications

Recent insights into the role of the contact pathway in thrombo-inflammatory disorders

Recent insights into the role of the contact pathway in thrombo-inflammatory disorders

Immunological Mechanisms Underlying the Genetic Predisposition to Severe Staphylococcus aureus Infection in the Mouse Model

Degradation of human kininogens with the release of kinin peptides by extracellular proteinases of Candida spp.

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