Activation of the complement, coagulation, fibrinolytic and kallikrein-kinin systems during attacks of hereditary angioedema

Ew, Nielsen; Johansen, Harald Thidemann; Høgåsen, K; Wuillemin, Walter A.; Ce, Hack; Te, Mollnes

doi:10.1016/0162-3109(96)00085-9

Cited by 35 publications

(30 citation statements)

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“…This effect is responsible for the development of edema and the movement of fluid from the intravascular space to the perivascular tissues. A significant activation of the terminal pathway of the C sequence was observed during the attack phase of hereditary AE as documented by the increased levels of SC5b-9 measured in patients during the attack phase [71]. These data together with the in vitro and in vivo observations indicating a clear permeabilizing activity of SC5b-9 [27] suggest the existence of a cross-talk between the C and the kinin systems in induction of vascular leakage during the acute episodes of AE.…”

Section: Angioedema As a Model Of Crosstalk Between Complement Andmentioning

confidence: 99%

Cross-talk between the complement and the kinin system in vascular permeability

et al. 2011

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The endothelium is a continuous physical barrier that regulates coagulation and selective passage of soluble molecules and circulating cells through the vessel wall into the tissue. Due to its anatomic localization, the endothelium may establish contact with components of the complement, the kinin and the coagulation systems which are the main, though not exclusive, inducers of vascular leakage. Although the complement and the kinin systems may act independently, increasing evidence suggest that there is a crosstalk that involve different components of both systems. Activation is required for the function of the two systems which are involved in pathological conditions such as hereditary and acquired angioedema (AE) and vasculitidis. The aim of this review is to discuss the contribution of complement and kinin systems to vascular leakage and the cross-talk between the two systems in the development of AE. This clinical condition is characterized by episodic and recurrent local edema of subcutaneous and submucosal tissues and is due to inherited or acquired C1-INH deficiency. Although the pathogenesis of the swelling in patients with AE was originally thought to be mediated by C2, ample evidence indicate bradykinin (BK) as the most effective mediator even though the possibility that both the complement and the kinin-forming systems may contribute to the edema has not been completely excluded. BK induces endothelial leakage interacting with B2 receptors but other molecules may be involved in the onset and maintenance of AE. In this review we shall discuss the role of B1 receptors and gC1qR/p33 in addition to that of B2 receptors in the onset of AE attacks and the importance of these receptors as new possible molecular targets for therapy.

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Section: Angioedema As a Model Of Crosstalk Between Complement Andmentioning

confidence: 99%

Cross-talk between the complement and the kinin system in vascular permeability

et al. 2011

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“…Bradykinin stimulates endothelial cell prostaglandin synthesis, leading to inactivation of platelet function [24,25], and increased superoxide [26] and nitric oxide formation [27]. Consequently bradykinin is linked with the pathophysiological processes that accompany inflammation and tissue damage which is thought to play a major role in the symptomatology of acute attacks in patients with angiodema [12,28].…”

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confidence: 99%

Binding of activated Factor XII to endothelial cells affects its inactivation by the C1‐esterase inhibitor

Schousboe

2002

European Journal of Biochemistry

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It is well known that activated Factor XII (FXIIa) and kallikrein are rapidly inactivated in plasma as a result of reaction with endogenous inhibitors. The purpose of this may be to prevent uncontrolled deleterious spreading and activation of target zymogens. Both FXII and the complex plasma prekallikrein/high molecular mass kininogen become activated when they bind, in a Zn 2+ -dependent manner, to receptors on human umbilical vein endothelial cells (HUVEC). The C1-esterase inhibitor (C1-INH) is by far the most efficient inhibitor of FXIIa. In the present study it has been investigated whether binding of FXIIa to HUVEC might offer protection against inactivation by C1-INH. It appeared that the relative amidolytic activity of purified FXIIa bound to the surface of HUVEC decreased according to the concentration of C1-INH in medium; however, the decrease was smaller than that measured for inactivation of FXIIa in solution. The secondary rate constant for the inactivation was 3-10-fold lower for cellbound than for soluble FXIIa. The inactivation was found to be caused by C1-INH binding to cell-bound FXIIa. Accordingly, the amidolytic activity of saturated amounts of cell-bound FXIIa was reduced in the presence of C1-INH and was theoretically nonexistent at physiological C1-INH concentrations. Amidolytic activity was, however, present on HUVEC incubated with plasma indicating that the endogenous C1-INH did not completely abolish the activity of FXIIa generated during the incubation period. This supports the hypothesis that binding to endothelial cells protects the activated FXII against inactivation by its major endogenous inhibitor. Hence, the function of FXII may be localized at cellular surfaces.

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“…Foram realizadas dosagens do nível sérico de C1-INH, C4 e C3 por nefelometria, com a utilização de anti-soro especí-fico para os componentes do complemento (Behring, Marburg, GE) 12,19 e ensaio hemolítico para avaliação das vias clássica e alternativa do sistema complemento (CH50 e APH50). Em resumo, o CH50 e o APH50 foram avaliados com a determinação da habilidade do soro em lisar eritrócitos de carneiro sensibilizados com anticorpo e eritrócitos de coelho, respectivamente.…”

Section: Exames Realizadosunclassified

“…Após diluição do soro, observa-se o valor correspondente a 50% de hemólise dos eritrócitos. A leitura da reação é feita em espectrofotômetro (CELM-E210D) a 541 nm para o CH50 e a 412 nm para o APH50 19,20 . Os valores de ambas as reações são obtidos após a construção …”

Section: Exames Realizadosunclassified

Angioedema hereditário: considerações sobre terapia

Chagas¹,

Arruk²,

Andrade³

et al. 2004

Rev. Assoc. Med. Bras.

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314CHAGAS KN ET AL. sendo mutações pontuais ou pequenas deleções ou inserções 3,4 . A maior função do C1-INH no corpo humano inclui a inibição direta da calicreína ativada, inibição do fator de Hageman (fator XII da cascata da coagulação) e prevenção da ativação do componente C1 do sistema complemento 5 . A diminuição da atividade de C1-INH permite a ativação de C1, com início da atividade, e consumo, de C4 e C2, resultando em diminuição de seus níveis séricos durante os ataques de HAE 6 . As formas de angioedema com deficiência de C1-INH são divididas em hereditárias e adquiridas. As hereditárias são decorrentes da produção deficiente do inibidor com função normal (tipo I) ou da produção de quantidade normal de C1-INH com função alterada (tipo II), o que corresponde a 85% e 15% dos casos, respectivamente. No tipo I, a região do gene rica em repetições Alu, sempre contém o gene defeituoso e isso explica porque pacientes do tipo I não produzem níveis normais de C1-INH e não há expressão de C1-INH. No tipo II, o defeito é usualmente localizado pró-ximo do sítio ativo ARG 444 ou no exon 8. Nas formas adquiridas (AAE) ocorre uma diminuição do C1-INH por aumento de seu catabolismo e, freqüentemente, estão associadas com doença linfoproliferativa e com a presença de anticorpo anti-C1-INH, sem doença de base detectável; a função de C1-INH está moderadamente diminuída e há resistência à reposição de C1 purificado 5,[7][8][9][10] . Uma redução acentuada na produção de C1q é considerada como marcador das formas adquiridas de angioedema, provavelmente por degradação através de ativação induzida por complexos anti-idiotipo/idiotipo 7 . Clinicamente, os pacientes com HAE usualmente tornam-se sintomáticos na segunda década de vida, apresentam grande variabilidade na freqüência dos episódios e a maioria dos ataques ocorre sem qualquer razão aparente, em três sítios principais: tecido subcutâneo, tratos gastrointestinal e RESUMO -OBJETIVOS. A primeira descrição clínica completa do angioedema hereditário (HAE) foi relatada por

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Activation of the complement, coagulation, fibrinolytic and kallikrein-kinin systems during attacks of hereditary angioedema

Cited by 35 publications

References 0 publications

Cross-talk between the complement and the kinin system in vascular permeability

Cross-talk between the complement and the kinin system in vascular permeability

Binding of activated Factor XII to endothelial cells affects its inactivation by the C1‐esterase inhibitor

Angioedema hereditário: considerações sobre terapia

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