Activation of the Kallikrein-Kinin System in Rocky Mountain Spotted Fever

Yamada, Tadataka; Harber, Philip; Pettit, George W; Wing, David A; Oster, Charles N.

doi:10.7326/0003-4819-88-6-764

Cited by 35 publications

(6 citation statements)

References 31 publications

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“…At the same time, increased levels of circulating fibrinogen likely refect enhanced synthesis of this acute phase protein. The presence of circulating C1 inhibitor–kallikrein complex and lower concentrations of prekallikrein indicate activation of the kallikrein–kinin system during spotted fever syndromes, for which the evidence for in vivo vascular injury/inflammation and onset of disseminated intravascular coagulation has also been described [116]. Enhanced urinary secretion of 11-dehydro-thromboxane B 2 , a major enzymatic metabolite of thromboxane A 2 , may largely be due to increased platelet thromboxane synthesis and activation during MSF [117].…”

Section: Correlations or Lack Thereof With The Findings From The Clinicmentioning

confidence: 99%

Host-Cell Interactions with Pathogenic Rickettsia Species

2009

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Pathogenic Rickettsia species are Gram-negative, obligate intracellular bacteria responsible for the spotted fever and typhus groups of diseases around the world. It is now well established that a majority of sequelae associated with human rickettsioses are the outcome of the pathogen's affinity for endothelium lining the blood vessels, the consequences of which are vascular inflammation, insult to vascular integrity and compromised vascular permeability, collectively termed ‘Rickettsial vasculitis’. Signaling mechanisms leading to transcriptional activation of target cells in response to Rickettsial adhesion and/or invasion, differential activation of host-cell signaling due to infection with spotted fever versus typhus subgroups of Rickettsiae, and their contributions to the host's immune responses and determination of cell fate are the major subtopics of this review. Also included is a succinct analysis of established in vivo models and their use for understanding Rickettsial interactions with host cells and pathogenesis of vasculotropic rickettsioses. Continued progress in these important but relatively under-explored areas of bacterial pathogenesis research should further highlight unique aspects of Rickettsial interactions with host cells, elucidate the biological basis of endothelial tropism and reveal novel chemotherapeutic and vaccination strategies for debilitating Rickettsial diseases.

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Section: Correlations or Lack Thereof With The Findings From The Clinicmentioning

confidence: 99%

Host-Cell Interactions with Pathogenic Rickettsia Species

2009

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“…and Salmonella, are able to bind and assemble contact factors on their surfaces and trigger the activation of the system [6,47]. An activation of the contact system by Staphylococcus aureus and Rickettsia rickettsii has also been described [7,48] although the bacterial proteins that promote the binding to the contact factors have not yet been identified. In addition, and as mentioned above, many bacterial proteinases have been described to cleave HK and release BK, and recently it has been reported that fungal pathogens also (Candida species) interact with factors of the contact system [49].…”

Section: Streptococcus Pyogenes or Thin Aggregative Fimbriae Expressementioning

confidence: 99%

Contact system activation in severe infectious diseases

Oehmcke

Herwald

2009

J Mol Med

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Hemostasis is a sensitive and tightly regulated process, involving vascular endothelium and blood cells, as well as factors of the coagulation and fibrinolytic cascades. In severe and invasive infectious diseases, the equilibrium between the procoagulant and anticoagulant status of the host may change dramatically and can induce life-threatening complications. A growing body of evidence suggests that the contact system, also known as the intrinsic pathway of coagulation or kallikrein/kinin system, participate in these processes. Contact activation leads to the release of the highly potent proinflammatory peptide bradykinin and initiates the intrinsic pathway of coagulation. Several studies have shown a systemic activation of the contact system in animal models of severe bacterial infections, and similar findings were also reported when monitoring patients suffering from sepsis, severe sepsis, or septic shock. Complications resulting from a systemic activation of the contact system are pathologically high levels of bradykinin, consumption of contact factors, and a subsequent induction of inflammatory reactions. These conditions may contribute to serious complications such as hypotension and vascular leakage. Here, we summarize the state of the art in this field of research with a focus on the contact system, and we also discuss a potential role for the contact system as a target for the development of novel antimicrobial strategies.

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“…Experimental evidence indicates that hostmediated pathogenic mechanisms, such as immunopathology (2,3,10,11,18), Shwartzman phenomenon-like blood coagulation (2,3,10,11,21), and inflammation, are not the primary mechanisms of injury in infection by Rickettsia rickettsii. Localized effects of kallikrein are probably events secondary to the primary pathogenic mechanism(s) (25). Occlusive vascular thrombosis is infrequent, occurs only in areas of localized rickettsial infection, and has not been demonstrated as a primary pathogenic mechanism (1,16,21).…”

mentioning

confidence: 99%

Human endothelial cell culture plaques induced by Rickettsia rickettsii

Walker¹,

Firth²,

Edgell³

1982

Infect Immun

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Primary cultures of human umbilical vein endothelial cells were inoculated with plaque-purified Rickettsia rickettsii. After adsorption of rickettsiae, monolayers were overlaid with medium containing 0.5% agarose. Small plaques appeared on day 4 postinoculation, and distinct 1to 2-mm plaques were observed on day 5. Plaquing efficiency was less than that of primary chicken embryo cells in the same medium. Human endothelial cell monolayers were susceptible to infection by R. rickettsii and underwent necrosis as demonstrated by supravital staining. The topographic association of endothelial cell necrosis and rickettsial infection in the plaque model confirmed the direct cytopathic effect of R. rickettsii on human endothelium. Uninfected cells appeared normal by supravital staining and transmission electron microscopy. This model offers the possibility of investigating rickettsial pathogenesis and mechanisms of enhanced severity of Rocky Mountain spotted fever in specific genetically determined conditions.

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Activation of the Kallikrein-Kinin System in Rocky Mountain Spotted Fever

Cited by 35 publications

References 31 publications

Host-Cell Interactions with Pathogenic Rickettsia Species

Host-Cell Interactions with Pathogenic Rickettsia Species

Contact system activation in severe infectious diseases

Human endothelial cell culture plaques induced by Rickettsia rickettsii

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