Complement and Its Component Fractions in Cerebrospinal Fluid in Inflammatory Cerebrospinal Diseases

Spicer, Sophie; Appelbaum, Emanuel; Rutstein, David D.

doi:10.1172/jci102081

Cited by 9 publications

(3 citation statements)

References 7 publications

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“…Early appearance of CMOA in CSF during bacterial meningitis -as opposed to viral meningitis -was paralleled by increases in C3 activity and C3 levels, which confirmed the presence of CHso [18] and various other complement components [24,41,42] in the CSF of patients with meningitis. The early appearance of CMOA in CSF was further correlated with changes in the protein concentrations in CSF early in the course of the disease.…”

Section: Discussionmentioning

confidence: 61%

Complement-Mediated Opsonic Activity in Normal and Infected Human Cerebrospinal Fluid: Early Response During Bacterial Meningitis

Zwahlen

Nydegger

Vaudaux

et al. 1982

Journal of Infectious Diseases

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A local defense mechanism in bacterial meningitis was evaluated in humans by measuring complement-mediated opsonic activity (CMOA) in normal and infected cerebrospinal fluid (CSF) with a complement-dependent phagocytic bactericidal assay. CMOA was absent in normal untreated CSF and remained undetectable in 20 samples of CSF from patients with viral meningitis and five samples from patients with acute meningococcemia. In contrast, 15 of 27 samples of CSF from patients with acute bacterial meningitis had a measurable CMOA, which was correlated with protein concentrations (P< 0.01) and C4 hemolytic activity (P< 0.001) in the CSF. A favorable outcome of bacterial meningitis was associated with the presence of CMOA in CSF (P < 0.005). Recovery was also correlated with higher levels of C4 (P < 0.01) and C3 (P < 0.05) in CSF and with lower concentrations of microorganisms in the sample of CSF collected at the time of admission (P< 0.01). Thus, CMOA, although absent in normal CSF, can appear in CSF during acute bacterial meningitis, particularly in patients who recover completely.Mortality and morbidity from acute bacterial meningitis are still high despite substantial progress in diagnosis and treatment [1][2][3]. The development and course of meningeal infection are governed by the complex interaction of many variables [4], including (1) microbial virulence factors such as encapsulation [5,6], (2) clearance of bacteria from the blood [7][8][9], (3) antibacterial mechanisms in the subarachnoid space [10], (4) anatomic and functional changes resulting from inflammation [11,12], and (5) antibiotic therapy. Because bacterial meningitis is in essence a closed-

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Section: Discussionmentioning

confidence: 61%

Complement-Mediated Opsonic Activity in Normal and Infected Human Cerebrospinal Fluid: Early Response During Bacterial Meningitis

Zwahlen

Nydegger

Vaudaux

et al. 1982

Journal of Infectious Diseases

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“…This raises the possibility that a soluble form of CD46 may be a useful therapeutic tool in preventing or reducing meningitis induced by this bacterial species. The pivotal role of complement in contributing to the inflammatory response in the infected brain has been recognized by clinicians and scientists since the first papers published in the 1930s and 1940s [90,91]. It is now clear that many, if not all, complement components are endogenously produced in the pathogen-infected brain and released into CSF [17,51,87].…”

Section: Complement and Bacterial Meningitismentioning

confidence: 99%

The role of the complement system in CNS inflammatory diseases

Stahel¹,

Barnum²

2006

Expert Review of Clinical Immunology

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Complement is an important component of both the innate and adaptive immune response that contributes to host defense in a variety of mechanisms, including inflammation, phagocytosis and cell lysis. Complement proteins are produced by all cell types in the CNS, and the same effector functions that protect the host from pathogens can mediate inflammation and tissue destruction in CNS diseases, leading to neurological deficits or even death. In the last 10 years, the development of complement inhibitors and a variety of animal models for CNS diseases has revealed that targeted inhibition of complement offers significant therapeutic potential. This review discusses the subtleties of targeted complement inhibition in CNS disease as an emerging therapeutic strategy.

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“…Nestes trabalhos em que este assunto foi discutido, com apreciações favoráveis ",2. publicaram os primeiros estudos sobre componente do complemento no LCR demonstrando que, em condições normais, não há atividade hemolítica do complemento total, porém sempre está presente a fração então denominada "fração globulínica ou peça média". Em 1949, pela primeira vez, Spicer e col. 88 fizeram a pesquisa dos quatro componentes do complemento no LCR, demonstrando que sempre um ou mais de um componente podia ser evidenciado em pacientes com doenças inflamatórias do sistema nervoso central. Nos casos de meningite bacteriana, em geral, os quatro componentes estavam presentes, sendo os componentes Cl e C4 os que se apresentavam em maior concentração, seguindo-se depois o componente C3 e, afinal, em menor concentração ou ausente, o componente C2.…”

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Demonstração do complemento total no liquido cefalorraqueano normal

Reis-Filho¹

1978

Arq. Neuro-Psiquiatr.

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Complemento ou alexína são as denominações dadas a uma substância do sangue que tem a propriedade de destruir células e bactérias sensibilizadas por um anticorpo específico. Entretanto, os fenômenos em relação com o complemento são tão diversos que é difícil formular uma definição concisa que inclua todas as suas atividades e manifestações. A dificuldade resulta naturalmente do fato do complemento não ser uma substância simples, mas uma série complexa de proteínas, algumas de natureza enzimática 58 . Como todas elas participam da citólise dependente do complemento, tornou-se habitual defini-lo tomando em consideração o seu poder de lesar membranas, conhecido por poder citolítico 04 . Os primeiros estudos analíticos sobre o complemento, feitos pelos autores antigos, permitiram considerá-lo constituído de dois componentes, o primeiro denominado "peça média ou fração globulínica\ e o segundo denominado "peça final ou fração albumínica", ambos termosensíveis. Posteriormente foi identificado o terceiro componente e finalmente o quarto componente, estes termoestáveis 1^22 . 30 . 36 .® 9 » 82 »™.O estudo eletroforético das proteínas constituintes do primeiro e do segundo componente 71 demonstrou que algumas expressões usadas eram incorretas, tendo sido proposta a abolição das designações "fração globulínica ou peça média" e "fração albumínica ou peça final" e aconselhada a uniformização da terminologia com os símbolos C 1, C 2, C 3 e C 4. Com o progresso dos conhecimentos, o complemento é atualmente considerado constituído por 9 componentes que se referem a onze proteínas 3 . Em 1968, o Comitê sobre Nomenclatura da Organização Mundial da Saúde recomendou uma modificação dos símbolos 4 designando o complemento total por C e os seus nove componentes por Cl, C4, C2, C3, C5, C6 C7, C8 e C9, de acordo com a ordem de participação na reação imunológica. O componente Cl divide-se em três sub-unidades denominadas Cl q , Cl r , e C1 B .O grupo dos últimos seis componentes (C3, C5, C7, C8 e C9) é também designado "conjunto C3" e, por esse motivo, com freqüência, muitos autores ainda continuam a se referir aos "quatro componentes" para indicar, como anteriormente, o complemento total, particularmente nos estudos com dosaResumo de tese de doutoramento. Escola Paulista de Medicina. 1977

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Complement and Its Component Fractions in Cerebrospinal Fluid in Inflammatory Cerebrospinal Diseases

Cited by 9 publications

References 7 publications

Complement-Mediated Opsonic Activity in Normal and Infected Human Cerebrospinal Fluid: Early Response During Bacterial Meningitis

Complement-Mediated Opsonic Activity in Normal and Infected Human Cerebrospinal Fluid: Early Response During Bacterial Meningitis

The role of the complement system in CNS inflammatory diseases

Demonstração do complemento total no liquido cefalorraqueano normal

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